The use of apitherapy and natural herbal medicines for combating toxoplasmosis has garnered major attention from many researchers. However, there is no available information regarding the potential use of a combination of propolis and wheat germ oil (WGO) in the treatment of toxoplasmosis. In the present study, the potential effects of propolis, WGO, and their combination in the treatment of chronic toxoplasmosis in Swiss albino mice were investigated. Following induction of chronic toxoplasmosis, the potential antiparasitic effects of these substances were evaluated by parasitological assessment and by counting of Toxoplasma cysts. Additionally, the effects of the treatments on parasite loads were analyzed using TaqMan real-time quantitative PCR targeting the Toxoplasma P29 gene followed by investigation of the major histopathological changes in the brain, uterus, and kidney. Interestingly, the combination of propolis and WGO significantly (P ≤ 0.05) decreased the parasite burden in experimental animals compared with burdens seen in groups treated with propolis or WGO alone. Furthermore, the quantification of the DNA concentrations of Toxoplasma P29 gene after the treatment with propolis and WGO revealed a reduction in parasite load in treated groups versus the control group (infected untreated animals). Importantly, the severity of histopathological lesions was significantly (P ≤ 0.05) improved following treatment with propolis and WGO. Collectively, the present study indicated a potential novel role for propolis and WGO as an active apitherapy and natural herbal medication for treating chronic toxoplasmosis, combat the disease, and which could also help overcome the side effects of chemical drugs.