Objective To determine the phytochemical screening, antioxidant activity and analgesic effect of crude ethanol extract of Waltheria ovata (W. ovata) Cav. root in mice. Methods Phytochemical screening was developed by color or the precipitate formation. The evaluation of antioxidant activity and total phenolic content were assessed using 2,2-diphenyl-1-picrylhydrazyl and Folin-Ciocalteu's reagent, respectively. The analgesic effect was determined by acetic acid and formalin test. Different doses of W. ovata (50, 150, 300 and 500 mg/kg body weight) were administered p.o. to various groups of mice. Results Phytochemical screening confirmed the presence of phenolic compounds, flavonoids, tannins, saponins, terpenoids and steroids. The antioxidant activity showed 25% for 0.1 μg/mL and was significantly higher (P < 0.01) than trolox and vitamin C, meanwhile, the total phenolic content (gallic acid equivalent) was 2 200 mg/g of dry extract. W. ovata demonstrated an independent analgesic effect in different experimental models, like, acetic acid (72.51%, P < 0.01) and formalin (first phase: 58.6%, P < 0.01; second phase: 91.5%, P < 0.01, respectively) at dose of 300 mg/kg, similar to diclofenac (5 mg/kg) and morphine (30 mg/kg), respectively. Conclusions W. ovata root's crude ethanol extract showed strong antioxidant activity and high phenolic content. The analgesic effect was demonstrated in two experimental models of pain implying that both peripheral and central mechanisms were involved. This might be due to the presence of various phytochemicals in the extract.