The present study was aimed to evaluate the effect of an aqueous extract of Tinospora cordifolia (AETC) against cyclophosphamide (CYP)-induced immunesuppression and systemic candidiasis in a murine model.Mice injected with a single dose of CYP (200 mg/kg) were treated with AETC at the doses of 25 and 100 mg/kg for 7 days. The severity of immunesuppression was evaluated by quantitative and qualitative changes in the leukocytes. To determine the antifungal activity, Candida albicans infected mice were treated with the formulations of AETC or fluconazole at various doses. The effectiveness of treatment was assessed by determining the survival rate, fungal burden, the organ index and liver inflammation parameters in the untreated or treated mice.CYP caused the weight loss and depletion of leukocytes, whereas AETC treatment resulted in the recovery of leukocytes. C. albicans infected mice treated with AETC at the doses of 50 and 100 mg/kg exhibited 30% and 50% survival rate, whereas the mice treated with fluconazole at a dose of 50 mg/kg showed 20% survival rate. Like to the survival data, the fungal load was found to be the lowest in the kidney tissues of mice treated with AETC at a dose of 100 mg/kg. Interestingly, mice infected with C. albicans demonstrated the improvement in the organ index and liver functioning after AETC treatment.These results suggest that AETC may potentially be used to rejuvenate the weakened immune system and eliminate the systemic candidiasis in mice.