Plecospermum spinosum Trecul. leaves collected from Eastern Ghats, India were assessed for antioxidant potential using the methanolic extract in vitro for free radical scavenging and phosphomolybdenum assays. The (2,2?-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)) (ABTS?+) assay exhibited potent free radical scavenging capacity at 100 ?g/mL (86.48 ? 0.8 %). Antimicrobial activity of the methanolic leaf extract greatly inhibited the growth of Pseudomonas aeruginosa (9 ? 0.7 mm) and Echinodontium tinctorium (12 ? 0.9 mm) when compared to the other tested pathogens. The hemolysis (%) was calculated for anti-inflammatory activity and the results showed dose dependent effects. The lowest inhibition (53.08 ? 1.5 %) was obtained for 800 ?g/mL extract when compared with control aspirin (90.41 ? 1.3 %) at the same concentration. Qualitative phytochemical tests confirmed the presence of triterpenoids, flavonoids, saponins, tannins, sterols, sugars and free aminoacids. Totally, 35 different phytochemical compounds were found using gas chromatography-mass spectrometry (GC?MS). Furthermore, the phenolics (70.34 ? 2.1 mg/g), flavonoids (164.28 ? 1.1 mg/g) and other metabolites were estimated quantitatively. These results exhibited considerable antioxidant, and antimicrobial activities due to the presence of bioactive phytochemicals. P. spinosum may be employed for the separation of novel bioactive metabolites with potential pharmaceutical activities.