Background: Rhinachantus nasutus (L.) Kurz (Rnz) is a plant that has the potential to be an antioxidant as well as an anti-diabetic medication. Traditional medicine has used preparations made from the roots, stems, and leaves of Rnz to treat diabetes. Aim: This study aimed determine the antioxidant and anti-diabetic potential of Rnz leaf extract by inhibiting the activity of dipeptidyl peptidase IV (DPP IV). Method: Rnz leaf samples were extracted using Ultrasound-Assisted Extraction (UAE). Following that, the antioxidant capacity was determined by trapping 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reduction antioxidant power (FRAP), and its potential as an antidiabetic was determined by inhibiting DPP IV activity. Results: The extraction yield of ethanol from Rkz leaves using the UAE method was 8.36%. The IC50 and EC50 values for the antioxidant capacity determined using the DPPH and FRAP methods were 97.34 ± 0.07 mg/L and 8.69 ± 0.02 mg/L, respectively. In addition, ethanolic leaf extract has potential as an antidiabetic through the mechanism of inhibition of DPP IV activity with an inhibition value of 43.05 ± 1.2%. The determination of compounds in the ethanolic extract of Rnz leaves using UHPLC-MS/MS QToF succeeded in identifying 65 compounds, with several compounds reported to be active as antidiabetic. These compounds are 1,3,7-trihidroxy-6-methoxy-4,5-diisoprenylxanthone (9), palmitic acid (10), 3,5-di(ethylthio)isothiazole-4-carboxaide (12), 4,8-dihydroxy-6-methoxy-3-methyl-3,4-dihydro-1H-isochromen-1-one (15), glaucine (20), 5-isopropyl-3,8-dimethylazulene-1-carbaldehhyde 1-(4-nitrophenyl)hydrazone (21), 2,5-anhydro-6-[(2-chloro-5-ethoxybenzoyl)amino]-4,6-dideoxy-4-(4-phenyl-1-piperazinyl)-D-galactitol (27), 2-(4-methylphenyl)-4-phenyl-2,3-dihydro-1,5-benzothiazepine (30), 1-palmitoylglycerol (32), (2S)-2-({1-[(4-fluorophenyl)ethyl]indazole-3-carbonyl)amino)-3-methylbutanoic acid (43), and ethyl 2-[(6-oxo-6H-benzo[c]chromen-3-yl)oxy]acetate (45). Conclusion: the ethanolic extract of the leaves of Rnz from the UAE has the potential as a source of antioxidants and antidiabetics. © RJPT All right reserved.