Bryonia species have traditionally been used as a diuretic and laxative, to reduce edema and relieve joint pain. B. alba roots are used especially to treat rheumatic pain and applied to painful joints in Turkish folk medicine. B. alba roots were extracted with n-hexane, ethyl acetate (EtOAc), and methanol, successively. The carrageenan-induced hind paw edema model and the Whittle method were used to evaluate the anti-inflammatory activity of the extracts in mice. The p-benzoquinone-induced abdominal constriction test and tail flick test were used to evaluate the antinociceptive activity of the extracts in mice. DPPH-radical-scavenging activity, ABTS radical–scavenging activity, total antioxidant activity, and hydroxyl radical– scavenging activity were assessed. Furthermore, the total phenolic and total flavonoid contents were calculated for all the extracts. The EtOAc extract prepared from B. alba roots had the most promising anti-inflammatory, antinociceptive, and antioxidant activities. Moreover, it had high phenolic and flavonoid contents. Therefore, B. alba roots could be alternative treatment method for rheumatic disorders.