Background and objective: Toxoplasmosis is a parasitic zoonose that is highly prevalent. The development of novel antiparasitic medications is highly challenging since the medications now used to treat toxoplasmosis have many side effects. This study aimed to identify the bioactive components in Salvia officinalis extract and their therapeutic efficacy against toxoplasmosis. Methodology: A total of 30 albino mice were divided into five groups: GI (non-infected); GII (infected without treatment); GIII, GIV and GV infected and treated groups with spiramycin, Salvia officinalis extract and combination of spiramycin and Salvia officinalis extract , respectively. Treatment starting from the 6th week post-infection and euthanized on the 8th week. For the study groups, parasitological, histopathological examinations and immunological analysis for and IL-10 and TNF-alpha levels was assessed. Moreover, Total phenolics content (TPC) of the extract was evaluated by Folin Ciocalteu assay and the total flavonoids content TFC were estimated usingAlCl3technique. Determination of the total antioxidant capacity by the phosphomolybdenum method and DPPH assay . Using RP-HPLC, phenolics and flavonoids of the extract were identified Results: The methanol extract show high antioxidant activity IC50 = 6.6µg/ml for DPPH and 400.30 mg AAE/g ext. respectively, this activity could be explained by the extract's high phenolic and flavonoid content.A comparison of the treated groups (GIII, GIV, and GV) with the control positive group (GII) revealed statistically significant variations in the parasite load, along with improvements in the histological changes. Of the test groups, the GV group also demonstrated the best improvement in parasitological and histological indicators. Comparing infected to the uninfected group, there was an increase in IL-10 and decrease in TNF-alpha (P< 0.0001). Significant down regulation of IL-10 and up regulation was seen in all treatment groups (GIII, GIV, and GV). The highest TNF-alpha and lowest IL 10 levels were found in the GV. These results depending on the bioactive compound of Salvia officinalis Conclusion: Spiramycin and Salvia officinalis showed a strong synergistic effect in treating toxoplasmosis.