Overall, the main objective of the current study was to screen the large chemical database against the CYP3A5 target for cardiovascular diseases through molecular docking, NIB screening, ML-based screening followed by pharmacokinetics and a toxicity assessment, molecular dynamics (MD) simulation, and molecular mechanics generalized Born surface area- (MM-GBSA) based binding free energy calculation. This evidence concerns the gene CYP3A5 and cardiovascular disorder.