Hyperlipidemia is a silent threat lurking in the blood-stream of millions worldwide. The nano-based platform has emerged as a promisingdrug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recentlyas an antihyperlipidemic candidate that could supersede the available antihyperlipidemicdrugs. Our goal was to optimize albumin-based nanoparticles loaded with Repaglinidefor parenteral delivery and conduct in silico and in vivo studies to explore the efficacyof Repaglinide for the management of hyperlipidemia along with its anti-diabetic effect.Methods: The impact of three independent factors, the albumin%, acetone volume, andglutaraldehyde/albumin, on the particle size, zeta potential, and entrapment efficiencywas investigated. Results: The optimized formulation was spherical, homogenous of an av-erage diameter (~181.86 nm) with a narrow size distribution, a zeta potential of −24.26 mV,and 76.37% as the EE%. The in vitro release of Repaglinide from nanoparticles showed asustained release pattern for 168 h, with an initial burst release after 24 h, and was fitted tothe Fickian diffusion mechanism. A molecular docking simulation showed a strong affinityto several protein targets, and the results were very promising, where Repaglinide gavea score of −7.70 Kcal/mol compared to Mevastatin (−6.71 Kcal/mol) and Atorvastatin(−8.36 Kcal/mol). On conducting in vivo studies on animal models, the optimized for-mula recorded a statistically significant decrease in the serum levels of total cholesterol,triglyceride, and low-density lipoproteins, with an increased high-density lipoprotein.Conclusions: This study suggested albumin nanoparticles as potential nanocarriers for theparenteral delivery of Repaglinide to ameliorate its antihyperlipidemic benefits, especiallyin diabetic patients