This study aimed to evaluate the total phenolic content (TPC), total flavonoid content (TFC), antioxidant capacity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activities, cytotoxicity and antimicrobial activity of the plant extracts with petroleum ether, chloroform and methanol solvents. All extracts showed noticeable amount of TPC, TFC, antioxidant and antimicrobial activities. The percentage yields of methanol, chloroform and petroleum ether extracts were 4.125%, 3.65% and 1.35% respectively. TPC of the whole part of the Portulaca quadrifida extracts varied between 4.9029±0.0087 mgGAE/g of methanol extract to 2.4914±0.0055mgGAE/g of petroleum ether extract. TFC varied from 2.335±0.0097 mgQE/g of extract (methanol) to 1.357±0.0035 mgQE/g extract (petroleum ether). The 2, 2-diphenyl-1-picrylhydrazyl (DPPH), (%)radical scavenging activity was varied between 46.7595% for methanolic extract to 22.86% of petroleum ether extract. Crude extracts of Portulaca quadrifida showed various degree of antimicrobial activity towards some standard and drug resistance microbial pathogens with mean zone of inhibition ranged from zero to 17mm. The plant also has zero toxicity level as compared with the standard feed of laboratory animals. Keywords: P. quadrifida, Cytotoxicity, total phenolic content (TPC), total flavonoid content (TFC), antioxidant activity and antimicrobial activity.