Objectives Fever is a condition when the body experiences an increase in average body temperature above normal level. Maja fruit (Crescentia cujete L.) contains chemical compounds including alkaloid, flavonoid, saponin, and terpenoid, suspected as potential antipyretics. Methods The study aimed to determine the antipyretic activity of ethanol extract of Maja fruit. A total of 25 male white mice of the DDY strain (20–30 g). These treatments divided into three groups with a dose extract of 125, 250, 500 mg/kg BW, standard groups of ibuprofen 400 mg/kg BW, and control groups of CMC-Na 1%. Mice were injected intraperitoneally with 0.1 cc of DPT vaccine-induced. Observations were made by measuring the rectal temperatures of mice using a digital thermometer before DPT vaccine injected or average temperatures, at 0 min (after DPT vaccine injected), 60, 120, 180, and 240 min after administering the test material. The differences between the positive control group, test group, and the negative control group were compared using statistical analysis using one-way variance analysis (ANOVA). The results were considered statistically when the value is (p<0.05). Results The above phytochemical screening results showed that alkaloids, flavonoids, and saponins were present in the Maja fruit powder and extract (C. cujete L.). Based on the results of the statistical analysis obtained, i.e., Group II was not significantly different from Group III and Group IV (p≤0.05) and was significantly different from Group I and Group V. Group I was significantly different from Group II, Group III and Group IV and was not significantly different from Group V (p≥0.05). Conclusions The study showed that Maja fruit mice’s antipyretic behavior at doses of 125, 250, and 500 mg/kg BW was confirmed as a result in reducing the body temperature of male mice. The 500 mg/kg BW dosage of Maja fruit extract (C. cujete L) effectively reduced fever.