D-3-O-methylchiroinositol isolated from the stem bark of Piliostigma thonningii was evaluated for analgesic, anti-inflammatory and anti-pyretic activities. The compound was screened for analgesic activity by the acetic acid-induced writhing and tail immersion tests. The anti-inflammatory activities were evaluated by the carrageenan-induced paw edema and Freund adjuvant-induced arthritis tests, while its anti-pyretic activity was determined using the yeast-induced pyrexia test. D-3-O-methylchiroinositol (10, 30 and 60 mg/kg) significantly (P < 0.01) reduced the number of acetic acid-induced writhing. In the tail immersion test, by 15, 45, 30 and 60 min post-treatment, tail withdrawal times in D-3-O-methylchiroinositol (30 and 60 mg/kg) were significantly (P < 0.01) longer compared to reaction times recorded in control group. The paw volumes obtained in the 60 mg/kg D-3-O-methylchiroinositol group by 1 h post-carrageenan injection were significantly (P < 0.05) lower than the paw volume of control rats. At 2 and 3 h, the paw volumes in the D-3-O-methylchiroinositol (10, 30 and 60 mg/kg) were significantly (P < 0.05) lower than paw volume of the control group. In the subacute phase of arthritis (18 h), paw volumes in D-3-O-methylchiroinositol (30 and 60 mg/kg) were significantly (P < 0.05 and P < 0.01, respectively) lower compared to paw volume in the control group. In the chronic phase (30 days) of arthritis, paw volumes in the D-3-O-methylchiroinositol (10, 30 and 60 mg/kg) were significantly (P < 0.01) lower than paw volume of the control group. The rectal temperatures of the 60 mg/kg D-3-O-methylchiroinositol were significantly lower at 1, 2, 3, 4 and 5 h post-yeast injection compared to those of the control. The findings of this study establish that D-3-O-methylchiroinositol has analgesic, anti-inflammatory and anti-pyretic activities.