Objective To explore the protective effect of hydroalcoholic extract of Portulaca oleracea L. (POHA) on ulcerative colitis (UC) and bone loss in mice. Methods The C57BL/6 mice were treated with dextran sulfate sodium (DSS) to establish UC model. A total of 50 mice were randomly assigned to including control group, DSS group, mesalazine (MS) group, low dose of POHA (POHAL) group, or high dose of POHA (POHAH) group. The control group freely drank drinking water, while the DSS, MS, POHAL and POHAH groups drank drinking water containing DSS for 8 weeks. Since the 2^nd week, the control group and DSS group were given normal saline by gavage. The MS group was given MS (100 mg/kg) by gavage. The POHAL group and POHAH group were given POHA (1 000 mg/kg and 2 000 mg/kg) by gavage, respectively. Body weight and disease activity index (DAI) were recorded and calculated every 2 d. On the 56^th day, the colon weight index, liver index, and spleen index were calculated, and the histological changes of colon were observed. Serum levels of bone metabolism markers and microstructure parameters of femur were detected. Results Compared with the control group, the DSS group showed significantly increased DAI score, colon weight index, liver index, and spleen index (all P＜0.01). The DSS group exhibited significant pathological damage in colon tissues and significantly increased serum levels of osteocalcin, C-terminal peptide of collagen type Ⅰ, and tartrate-resistant acid phosphatase 5b (P＜0.01). The bone loss was significant in the DSS group, manifested by markedly decreased bone mineral density (BMD), bone tissue volume to tissue volume ratio (BV/TV), trabecular bone number (Tb.N), and trabecular bone thickness (Tb.Th), and markedly increased bone surface to bone volume ratio (BS/BV) and trabecular bone separation (Tb.Sp) (P＜0.05 or P＜0.01). Compared with the DSS group, the BMD, BV/TV, Tb.N and Tb.Th of the femur in the MS group and POHAH group of mice were all increased (P＜0.05 or P＜0.01), the BS/BV all decreased (P＜0.05 or P＜0.01), and the Tb.Sp all decreased without significant differences (all P＞0.05). The above bone microstructure parameters in the POHAL group showed no significant differences compared with those in the DSS group (all P＞0.05). Conclusion POHA has protective effect on DSS-induced UC and bone loss, and the mechanism may be related to the inhibition of hyperactive bone metabolism.