Abstract: Traditionally, Plumbago zeylanica Linn. is used for the treatments of intestinal warms and skin diseases in Ethiopia. The main objective of this study was to investigate the antioxidant and antimicrobial activities of the crude extract of Plumbago zeylanica root. In this study, two different antioxidant activity quantification methods: 2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH) and reducing power, FRAP including total phenolic, TPC assays of crude extract of P. zeylanica root were performed. The extracts showed significant activities in all antioxidant assays in a concentration dependent manner. Crude extract was found to possess higher ferric reducing activity (ascorbic acid equivalents 227.011±0.042 mg AA/100 g) and DPPH activity of 156.00±0.048 mg AAE/100 g. Strong correlation of TPC with AEACDPPH and AEACFRAP (R = 0.9745 and R = 0.96652, respectively) implied that compounds in the extract were capable of scavenging the DPPH free radical and reducing ferric ions. The free radical scavenging activity and the reducing capacity of the extract in the present study may serve as a significant indicator of its potential antioxidant activity. Antimicrobial activities evaluation of crude extract against S. aureus ATCC, MRSA, S. pneumoniae ATCC, S. pneumoniae (clinical) (gram positive bacteria), K. pneumoniae (clinical), S. boydii ATCC, E. coli ATCC, E. coli (clinical) (gram negative bacteria) and antifungal activity against C. albicans (clinical) (fungus) were also showing a higher antimicrobial activity of the crude extract. The findings of this study support the view that P. zeylanica plant is a promising source of potential antioxidants and may be effective as preventive agent in the pathogenesis of some diseases.