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The present study aimed to investigate the phytochemical profile and antimicrobial efficacy of Premna tomentosa bark extracts using various solvents, including methanol, chloroform, ethyl acetate, and petroleum ether. Qualitative phytochemical screening revealed that methanol was the most effective solvent, extracting a broad range of compounds such as alkaloids, flavonoids, phenols, tannins, glycosides, cardiac glycosides, coumarins, quinones, and resins. Chloroform also demonstrated significant efficacy in extracting alkaloids and flavonoids. Quantitative analysis showed that methanol extracts contained the highest concentrations of alkaloids (480 mg/g), flavonoids (510 mg/g), phenols (428 mg/g), and tannins (340 mg/g), indicating its superior extraction capabilities. The antibacterial activity was assessed using the paper disc diffusion method against four bacterial strains: Pseudomonas fluorescens, Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. The methanol extract exhibited the most potent antibacterial activity, with inhibition zones ranging from 4 mm to 7 mm. Chloroform and ethyl acetate extracts also showed significant inhibition, while petroleum ether was the least effective. In the antifungal assays, the methanol extract again demonstrated the highest efficacy, particularly against Fusarium oxysporum NCIM1008, Sclerotium rolfsii NCIM 1084, and Phytophthora infestans MTCC 8707. The inhibition percentages were highest with methanol (50% against Fusarium oxysporum and Phytophthora infestans), followed closely by chloroform (52% against Phytophthora infestans), and moderate inhibition was observed with ethyl acetate and petroleum ether. These results indicate that Premna tomentosa bark extracts, particularly those obtained using methanol, possess significant antibacterial and antifungal activities, potentially due to the high concentration of bioactive compounds extracted. This study supports the use of Premna tomentosa as a source of natural antimicrobial agents and underscores the importance of solvent selection in phytochemical extraction.