Background: Pancreatic lipase (PL), the principal enzyme catalyzing the hydrolysis of dietary triacylglycerols in the intestinal lumen, is pivotal for efficient lipid absorption and plays a central role in metabolic homeostasis. Enhanced PL activity promotes excessive lipid assimilation and contributes to positive energy balance, key pathophysiological mechanisms underlying the escalating global prevalence of obesity—a complex, multifactorial condition strongly associated with metabolic disorders, including type 2 diabetes mellitus and cardiovascular disease. Inhibition of pancreatic lipase (PL) constitutes a well-established therapeutic approach for attenuating dietary lipid absorption and mitigating obesity. Methods: With the aim to identify putative PL inhibitors, a Structure-Based Virtual Screening (SBVS) of PhytoHub database naturally occurring derivatives was performed. A refined library of 10,404 phytochemicals was virtually screened against a crystal structure of pancreatic lipase. Candidates were filtered out based on binding affinity, Lipinski’s Rule of Five, and structural clustering, resulting in six lead compounds. Results: In vitro, enzymatic assays confirmed theoretical suggestions, highlighting Pinoresinol as the best PL inhibitor. Molecular dynamics simulations, performed to investigate the stability of protein–ligand complexes, revealed key interactions, such as persistent hydrogen bonding to catalytic residues. Conclusions: This integrative computational–experimental workflow highlighted new promising natural PL inhibitors, laying the foundation for future development of safe, plant-derived anti-obesity therapeutics.

G-quadruplexes (G4s) are distinctive four-stranded nucleic acid structures formed by guanine-rich sequences, making them attractive targets for drug repurposing efforts. Modulating their stability and function holds promise for treating diseases like cancer. To identify potential drug candidates capable of interacting with these complex DNA formations, docking studies and molecular dynamics (MDs) simulations were conducted. Our analysis revealed kanamycin’s ability to bind to various G4 structures, offering valuable insights into its potential as a modulator of G4 activity. Kanamycin exhibited favorable interactions with both parallel and hybrid G4 topologies in human structures, suggesting a broader mechanism of action for aminoglycosides. These findings may also shed light on aminoglycoside-associated toxicities, indicating that their effects might extend to binding non-ribosomal RNA structures. In summary, this research highlights kanamycin’s potential as a promising tool for influencing G4 dynamics, paving the way for innovative therapeutic strategies targeting G4-related pathways.