Typhoid fever is a disease caused by Salmonella Typhi and commonly treated by an antimicrobial agent such as cotrimoxazole. On the other hand, herbal usage has risen as an adjunctive therapy to treat many diseases. Curcuma (Curcuma domestica) is a commonly used herb which consists of curcumin as its major active compound. Curcumin has been known for its antimicrobial effect, but there is no proof regarding the usage of curcumin and cotrimoxazole together. This research was conducted by using typhoid fever model in mice infected by Salmonella Typhimurium. Each animal was treated with curcumin, cotrimoxazole, or both. Ileum, spleen, and liver of each animal were isolated and cultured. We found that curcumin-cotrimoxazole combination therapy lowered the antimicrobial effectivity of cotrimoxazole in both intraintestinal and extraintestinal organs. We conclude that curcumin-cotrimoxazole combination therapy in typhoid fever has to be reconsidered.