Background: Herbal products encompass a wide range of natural substances that show great potential as therapeutic materials. Consequently, there has been a substantial investigation into the therapeutic potential of numerous plant species in recent times. The present study sought to determine the components and assess the antioxidant, antilipase, α-amylase, and α-glycosidase enzyme inhibitory activities of Stiefia multicaulis (Vahl) Sojak Vahl hexane, acetone, methanol, and aqueous fractions. Methods: Standard pharmacopeia methods were used to conduct screenings for both quantitative and qualitative phytoconstituents. The lipase, α-amylase, and α-glycosidase enzyme inhibitory activities were assessed using established reference methods. In addition, the antioxidant activity was assessed using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Results: The screening methods of pharmacopeias revealed that S. multicaulis contains a wide range of secondary metabolites, especially tannins. However, the most potent antioxidant, antilipase, α-glucosidase, and α-amylase inhibitory activities were acetone fraction, hexane, methanol, and aqueous S. multicaulis fractions, respectively. Conclusion: The current study outcomes are the first on the α-amylase, lipase, α-glucosidase inhibitory activities of S. multicaulis four solvent fractions. Further investigations are needed to assess the in vivo potential of these plant fractions in animal models.