<p><i>Annona squamosa Linn</i>., a widely cultivated fruit-bearing tree of the Annonaceae family, has been long revered for its diverse medicinal properties, encompassing insecticidal, microbicidal, anticancer, antidiabetic, anti-obesity, and molluscicidal effects. Nonetheless, its potential in addressing hypolipidemia, characterized by aberrant lipid levels, remains unexplored till date. To bridge this knowledge gap, our study delved into the therapeutic panorama of Annona squamosa by meticulously scrutinizing selected heterocyclic compounds via a comprehensive computational analysis, specifically targeting hypolipidemia. Through an exhaustive appraisal of <i>A. squamosa’s</i> phytochemical composition, heterocyclic compounds exhibiting potential lipid-modulating attributes were identified. Ten compounds underwent molecular docking, dynamics simulation, MMGB-SA, and ADMET analysis. In silico molecular docking simulations revealed the exceptional potency of sitosterol and stigmasterol, indicating favorable interactions with selected lipid metabolism-regulating proteins. The protein-ligand complexes demonstrated high stability during molecular dynamics simulations. These findings shed light on the therapeutic potential of <i>A. squamosa</i> for hypolipidemia treatment and encourage further research. The computational analysis serves as a foundation for drug discovery and development, presenting a novel approach to combat lipid-related disorders. Overall, this study deepens our understanding of <i>Annona squamosa’s</i> medicinal properties and underscores the importance of computational-based approaches in pharmaceutical advancements.</p>