Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound extracted and isolated from green tea, which has a variety of important biological activities in vitro and in vivo, including anti-tumor, anti-oxidation, anti-inflammation and lowering blood pressure. The aim of the present study was to investigate the protective effect of EGCG against secondary osteoporosis in a mouse model via the Wnt/beta-catenin signaling pathway. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to analyze runt-related transcription factor 2 and osterix mRNA expression, and the protein expression of cyclin D1, Wnt and beta-catenin, and suppressed peroxisome proliferator-activated receptor protein expression. The protective effect of EGCG against secondary osteoporosis was examined and its potential mechanism was analyzed. Treatment with EGCG significantly decreased serum calcium, urinary calcium, body weight and body fat, and increased leptin levels in mice with secondary osteoporosis. In addition, EGCG treatment significantly inhibited the structure score of articular cartilage and cancellous bone in proximal tibia metaphysis in mice with secondary osteoporosis. Treatment also significantly decreased alkaline phosphatase activity, runt-related transcription factor 2 and osterix mRNA expression. EGCG also significantly induced the protein expression of cyclin D1, Wnt and beta-catenin, and suppressed peroxisome proliferator-activated receptor gamma protein expression in mice with secondary osteoporosis. Taken together, these results suggest that EGCG may be a possible new drug in clinical settings.