Alpha-mangostin ($\alpha$-MG) is a prenylated xanthone extracted from the pericarp of the mangosteen tree (Garcinia mangostana) fruit. The compound exhibits a broad range of therapeutic properties, such as anti-inflammatory, antioxidative, and antimicrobial activity. This review highlights new findings in antibacterial studies involving $\alpha$-MG, demonstrates its potent activity against Gram-positive bacteria, including Staphylococcus and Enterococcus genera, and describes the antibacterial mechanisms involved. Most cited literature comes from 2020 to 2025, highlighting the topic’s relevance despite limited new publications in this period. The primary antibacterial mechanism of $\alpha$-MG consists of the disruption of the bacterial membrane and increased bacterial wall permeability, leading to drug accumulation and cell lysis. Other mechanisms include genomic interference and enzyme activity inhibition, which impair metabolic pathways. $\alpha$-MG can also disrupt biofilm formation, facilitate its removal, and prevent its maturation. Furthermore, $\alpha$-MG presents strong synergistic action with common antibiotics and other phytochemicals, even against drug-resistant strains, facilitating infection treatment and allowing for reduced drug dosage. The main challenge in developing $\alpha$-MG-based drugs is their low aqueous solubility; therefore, nanoformulations have been explored to improve its bioavailability and antibacterial stability. Extended research in this direction may enable the development of effective antibacterial and anti-biofilm therapies based on $\alpha$-MG.