Since ancient times, animal venoms have been used to treat a variety of diseases, and today, more investigations are needed to study and develop natural products to prove their beneficial effects in cancer treatment. It is believed that bee venom (BV) has various biological activities including analgesic, antioxidant, anti-inflammatory, anti-cancer, and anti-bacterial effects. Hence, the current study was conducted with the aim of investigating the anti-tumor, anti-oxidative, and anti-inflammatory effects of BV in C26 colon carcinoma-bearing mice model. Here, we stablished the C26 colon cancer mice model and evaluated the effects of BV on the mRNA expression of Cox-2, IL-6, IL-1β, and TNF-α in mice tumor tissues using quantitative real-time PCR (qRT-PCR) method. To investigate the anti-oxidative effects of BV, the superoxide dismutase (SOD), malondialdehyde (MDA), and total thiol content were measured by colorimetric assay. Mice treated with BV exhibited a significant reduction in the tumor growth and a longer median survival comparing to the control group. Treatment with BV significantly downregulated the mRNA expression of Cox-2, IL-1β, IL-6, and TNF-α in comparison with the control group. In addition, a marked decrease in MDA content and an increase in SOD and total thiol levels were also observed in the BV-treated group comparing with control group. Taken together, BV with its anti-tumor, antioxidant, and anti-inflammatory effects could be a promising candidate for development as a therapeutic option for colorectal cancer treatment.