Background: Meroterpenoids represent a remarkably diverse class of natural secondary metabolites, some of which are synthesized via terpenoid biosynthetic pathways. Over the past ten years, these compounds have gained interest because of their wide range of biological activities, such as anti-cholinesterase, COX-2 inhibitory, antibacterial, antiviral, antidiabetic, antioxidant, anti-inflammatory, antineoplastic, and cardioprotective properties. This review aims to consolidate the recognized neuroprotective effects of meroterpenoids from marine and terrestrial fungi. Methods: Data compiled from several databases, including PubMed, Science Direct, Scopus, and Google Scholar, include articles published since 2000 using keywords such as “neuroprotective”, “fungi”, “mushroom”, “marine sponge”, “neurodegeneration”, and “dementia” in connection with “meroterpenoids”. Results: Meroterpenoids modulate different cell signaling pathways and exhibit different and often combined mechanisms of action to ameliorate neuronal damage and dysfunction. Reported activities include anti-cholinesterase, antioxidant, BACE1 inhibition, and anti-inflammatory activities, all of which have potential in the treatment of dementia associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Conclusions: Meroterpenoids have the potential to be developed as effective tools for neuropathological diseases. Ongoing research to elucidate the various neuroprotective pathways remains essential and requires further investigation.

Alzheimer’s disease continues to be one of the most urgent neurodegenerative conditions, with acetylcholinesterase (AChE) inhibitors serving as a fundamental component of contemporary treatment approaches. Growing evidence underscores that marine ecosystems are a rich source of structurally varied and biologically active natural products exhibiting anticholinesterase properties. This review presents a thorough synthesis of marine-derived metabolites—including those sourced from bacteria, fungi, sponges, algae, and other marine life—that demonstrate inhibitory effects against AChE and butyrylcholinesterase (BuChE). Numerous compounds, such as meroterpenoids, alkaloids, peptides, and phlorotannins, not only show nanomolar to micromolar inhibitory activity but also reveal additional neuroprotective characteristics, including antioxidant effects, anti-amyloid properties, and modulation of neuronal survival pathways. Despite these encouraging findings, the transition to clinical applications is hindered by a lack of comprehensive pharmacokinetic, toxicity, and long-term efficacy studies. The structural variety of marine metabolites provides valuable frameworks for the development of next-generation cholinesterase inhibitors. Further interdisciplinary research is essential to enhance their therapeutic potential and facilitate their incorporation into strategies for addressing Alzheimer’s disease and related conditions.

(1) Background: Meroterpenoids represent a remarkably diverse class of natural secondary metabolites, some of which are synthesized via terpenoid biosynthetic pathways. Over the past ten years, these compounds have gained interest because of their wide range of biological activities, such as anti-cholinesterase, COX-2 inhibitory, antibacterial, antiviral, antidiabetic, antioxidant, anti-inflammatory, antineoplastic, and cardioprotective properties. This review aims to consolidate the recognized neuroprotective effects of meroterpenoids from marine and terrestrial fungi. (2) Methods: Data compiled from several databases, including PubMed, Science Direct, Scopus and Google Scholar, include articles published since 2000 using keywords such as “neuroprotective”, “fungi”, “mushroom”, “marine sponge” “Alzheimer's”, and “dementia” in connection with “meroterpenoids”. (3) Results: The reviewed studies indicate that further investigation is required, suggesting that meroterpenoids may serve as promising therapeutic agents for neurodegenerative diseases by modulating different cell signaling pathways and exhibiting different and often combined mechanisms of action to ameliorate neuronal damage and dysfunction. Reported activities include anti-cholinesterase, antioxidant, BACE1 inhibition and anti-inflammatory, all of which have potential in the treatment of dementia associated with neurodegenerative diseases such as Alzheimer's and Parkinson's. The advantages of slowing disease progression, enhancing cognitive abilities, and elevating quality of life have been emphasized. (4) Conclusions: Meroterpenoids have the potential to be developed as effective tools for neuropathological diseases. Ongoing research to elucidate the various neuroprotective pathways remains essential and requires further investigation.