The increasing prevalence of antimicrobial resistance and oxidative stress-related disorders necessitates the search for alternative, plant-based therapeutic agents. This study evaluated the phytochemical, antioxidant and antimicrobial activity of Hymenocardia acida and Phyllantus amarus extracts against clinical isolates. The phytochemical composition was evaluated using qualitative and quantitative assay, antioxidant activity using DPPH and FRAP assay, antimicrobial efficacy of Hymenocardia acida and Phyllanthus amarus leaf extracts, using methanol, chloroform, and n-hexane as extraction solvents and MIC was evaluated using microbroth diffusion method. Qualitative screening revealed the presence of key secondary metabolites such as alkaloids, flavonoids, phenols, tannins, saponins, terpenoids, and cardiac glycosides in varying abundance. Quantitative analysis showed that P. amarus methanol extract had the highest total phenol content (125.51 ± 0.80 mg GAE/g), while H. acida recorded higher flavonoid content (41.50 ± 0.09 mg QE/g). Antioxidant assays demonstrated that the methanol extracts of both plants exhibited the strongest DPPH radical scavenging activity, with P. amarus showing 78.15% inhibition and H. acida 57.64% at 500 µg/mL. The FRAP results further confirmed the antioxidant capacity, particularly in the methanol extracts. Antimicrobial evaluation against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida spp. revealed that methanol extracts were most effective, with inhibition zones up to 12.4 mm for P. amarus and 10.8 mm for H. acida. The Minimum Inhibitory Concentration (MIC) tests highlighted the chloroform fraction of H. acida as the most potent, with MICs as low as 3.12 µg/mL against S. aureus and Klebsiella spp. These findings underscore the therapeutic potential of both Hymenocardia acida and Phyllanthus amarus, supporting their ethnomedicinal uses and providing a scientific basis for their development into natural antioxidant and antimicrobial agents. Further studies on compound isolation and in vivo validation are recommended.