The quest for novel anti-diabetic medication from medicinal plants is very important since they contain bioactive phytochemicals that offer better activity and safety compared to conventional therapy. In the present study, in vitro, in vivo and in silico approaches were explored to evaluate the anti-inflammatory, antioxidants, and hypoglycemic activities of the crude methanol extract of Azanza garckeana pulp. Our in vitro analysis revealed that the extract contains total phenols (260.80 ± 2.23 mg/100 g) and total flavonoids (10.28 ± 1.29 mg/100 g) contents, and demonstrated dose-dependent in vitro antioxidants activities in; DPPH (IC50 =141.30 ± 1.64 µg/mL), FRAP (IC50 =155.07 ± 1.03 µg/mL), LPO (IC50 =184.96 ± 2.01 µg/mL), and ABTS (IC50 =162.56 ± 1.14 µg/mL) assays; anti-inflammatory activities in: membrane stabilization (IC50 =141.34 ± 0.46 µg/mL), protein denaturation (IC50 =203.61 ± 2.35 µg/mL) and proteinase activities (IC50=f 171.35 ± 1.56 µg/mL) assays; and hypoglycemic activities in: α- amylase (IC50 277.85 ± 2.51 µg/mL), and glucose uptake by yeast cells assays. In vivo analysis revealed that the extract exhibited dose-dependent anti-inflammatory, hypoglycemic activities and improved the weight gain in STZ-induced diabetic rats. In addition, the extract attenuated oxidative stress and increased the activities of SOD, catalase, GSH while depleting the level of LPO in STZ induced diabetic rats. Consequently, the liquid chromatography mass spectrometry (LC-MS) characterization of A. garckeana pulp, revealed the presence of 2-Hexadecen-1-ol,3,7,11,15-tetramethyl-,(2E,7 R,11 R)-, nonyl flavanone, testolactone and 6-(Benzyloxy)− 4,4-Dimethyl-2-Chromanone. These compounds were subjected to pharmacoinformatics analysis among which testolactone and 6-(Benzyloxy)− 4,4-Dimethyl-2-Chromanone demonstrated the best drug-likeness, pharmacokinetics, and also exhibited potential hypoglycemic and anti-inflammatory properties. Altogether, the present study provides preclinical evidence of the antioxidant, anti-inflammatory and antidiabetic activities of A. garckeana extract suggesting its potential applications for the development of alternative therapy for diabetes and its associated inflammatory condition.