OBJECTIVE: Mussaenda pubescens (Rubiaceae) is a medicinal plant, traditionally utilized for gastrointestinal, febrile, and reproductive ailments. This study was aimed at analyzing the antioxidant capacity and antihyperlipidemic efficacy of the methanolic extract of M. pubescens in a high-cholesterol diet-induced hyperlipidemic mouse model. METHODS: Twenty-five Swiss albino mice were randomly subdivided into five groups of five mice each: normal control, disease control, atorvastatin (20 mg/kg), 200 mg/kg of the extract, and 400 mg/kg of the extract. Hyperlipidemia was achieved by feeding a high-fat diet for 28 days before the oral treatment was given for 12 consecutive days. The serum lipid profile and DPPH radical scavenging activity were then analyzed. RESULTS: The extract improved the lipid abnormalities when compared with untreated hyperlipidemic mice (p < 0.05). At 200 mg/kg, LDL-C decreased to 11.25 ± 1.05 mg/dL, whereas the 400 mg/kg dose reduced TG and VLDL-C to 140.50 ± 6.50 and 28.10 ± 1.30 mg/dL, respectively. Atorvastatin demonstrated greater lipid normalization. The antioxidant activity was also shown by the extract with a DPPH assay, with an IC50 value of 235.64 μg/mL. CONCLUSION: The methanolic extract of M. pubescens exhibits potent antihyperlipidemic and antioxidant activities, validating its potential as a promising phytotherapeutic candidate for the management of hyperlipidemia and oxidative stress-associated metabolic disorders. Further in-depth phytochemical profiling and mechanistic studies are required for better evaluation of this extract.