Inflammation, fever, and pain can be associated with several diseases, and the synthetic drugs used in the treatment of these conditions often have severe side effects. As a result, there is a need for effective, economical, and safe alternative drugs, such as those derived from medicinal plants. Therefore, this study aimed to evaluate the anti-inflammatory, antipyretic, analgesic, and antioxidant activities of Castanopsis costata leaf fractions (CcLF), as well as its acute toxicity. For anti-inflammatory, antipyretic, and analgesic tests, rats were given CcLF (WFCC, EAFcC, and n-HFCC) at 50 and 100 mg/kg, diclofenac sodium (10 mg/kg), paracetamol (150 mg/kg), aspirin (100 mg/kg), and tramadol (20 mg/kg). For the antioxidant activity test, various concentrations of CcLF were used ranging from 25 to 200 μg/mL. This study also looked into whether there could be any acute toxicity and histopathology of the liver, stomach, and kidneys in experimental animals. The administration of CcLF significantly inhibited the increase in foot edema volume, and CcLF (EAFCC at 100 mg/kg) considerably decreased rectal temperature and was proportional to the standard drug paracetamol, and significantly inhibited pain sensation in various models. Additionally, CcLF showed strong antioxidant activity, and its administration at a dose limit of 5000 mg/kg/day did not show any toxic effects or death in test animals. The results of the current confirmed that CcLF has demonstrated anti-inflammatory, antipyretic, analgesic, and antioxidant properties in experimental models, and is practically non-toxic.