Inflammation, fever, and pain are common symptoms that can adversely affect overall health and quality of life. Hedyotis capitellata Wall. ex G. Don (Rubiaceae) is a traditional herbal medicine that alleviates these symptoms. However, scientific evidence supporting its effectiveness remains limited. Therefore, this study aimed to evaluate the potential of H. capitellata in controlling pain, fever, and inflammation. The analgesic properties of H. capitellata, were assessed using acetic acid and formalin tests. Paw edema induced by 1% carrageenan was used to evaluate anti-inflammatory activity, while the yeast-induced fever model was employed to investigate the antipyretic activity of H. capitellata. Ethanol leaf extract of H. capitellata (EHCW) was administered at different doses of 200, 250, and 300 mg/kg, with positive control groups receiving aspirin, tramadol, indomethacin, and paracetamol, and a negative control group receiving normal saline. The results showed that ethanol leaf extract of H. capitellata exhibited the highest analgesic activity (p < 0.05) at 300 mg/kg. It also demonstrated significant inhibition of paw edema (p < 0.05), at 300 mg/kg. Ethanol leaf extract of H. capitellata demonstrated a significant reduction (p < 0.05) in rectal temperature in the yeast-induced fever model, with the maximum effect at 300 mg/kg. In conclusion, the study demonstrated the potential of H. capitellata in treating conditions related to inflammation, pain, and fever.