Use of multi-plant extracts against infectious diseases is increasing in rural Tanzania. The study evaluated this ethnomedicinal practice by using mixed root extracts of Carisa edulis, Ximenia caffra, Harrisonia abyssinica and Euclea natalensis against single extracts of the same plants. Disc diffusion assay and Tube dilution techniques were used to compare bioactivity of plant extracts in-vitro. The ANOVA test indicated significant difference (P < 0.05) between these extracts types. Multi-plant extracts had inhibition zones of up to 26 mm as compared to 14 mm for single extracts. Minimum Inhibitory Concentration for multi-plant extract was 8.3 microg/ml against 69 microg/ml for single extracts. Multi-plant extracts inhibited all the five test bacterial species while single extracts inhibited three species. Eight out of ten multi-plant extracts (80%) were bactericidal while only two out of four single extracts (50%) were bactericidal. Generally, multi-plant extracts were more superior over single plant extracts and could be developed into more potent antibiotics against resistant pathogens.