This study investigated and compared the antioxidative, antidiabetic effects and possible active compounds present in various solvent extracts of fruit, leaf and stem of Aframomum melegueta (Rosc.) K. Schum. Samples were sequentially extracted using solvents of increasing polarity. They were investigated for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing power, inhibition of hemoglobin glycosylation, α-amylase and α-glucosidase activities as markers of in vitro antidiabetic effects at various doses (30-240 μg/mL). Possible compounds were analyzed using gas chromatography-mass spectrometry (GC-MS) analysis. From the results, fruit ethanolic (EtOH) extract showed higher total polyphenol (12.52 ± 0.13 mg/g GAE) and flavonoid (4.92 ± 0.12 mg/g QE) contents compared to other extracts. Similarly, for all the in vitro models used in this study, fruit EtOH extract exhibited lower IC50 values compared to other extracts, comparable to standards used in this study (DPPH 0.04 ± 0.01 mg/mL; ascorbic acid: 0.03 ± 0.02 mg/mL; gallic acid: 0.05 ± 0.01 mg/mL; hemoglobin glycosylation: 0.7 2 ± 0.03 mg/mL; gallic acid: 0.20 ± 0.01 mg/mL; α-amylase: 0.62 ± 0.01 mg/mL; acarbose: 4.91 ± 0.80 mg/mL; α-glucosidase: 0.06 ± 0.01 mg/mL; acarbose: 0.34 ± 0.02 mg/mL). Additionally, EtOH extract of the fruit demonstrated significantly (p < 0.05) higher reducing potentials of Fe3+ to Fe2+ compared to other solvent extracts. The GC-MS analysis of fruit and leaf EtOH extracts revealed the presence of some phenolics and other fatty acids derivatives as possible compounds present. Conclusively, fruit EtOH extract exhibited higher antioxidative and antidiabetic effects compared to other solvent extracts in vitro and thus require further work to fully validate these effects in vivo.