Dersimelagon is an orally administered selective melanocortin-1 receptor agonist being investigated for treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis. Dersimelagon is extensively metabolized in the liver, and potential recipients may have liver dysfunction. Further, effects of renal impairment on pharmacokinetic properties should be established in drugs intended for chronic use. Two separate studies (ClinicalTrials.gov: NCT04116476; NCT04656795) evaluated the effects of hepatic and renal impairment on dersimelagon pharmacokinetics, safety, and tolerability. Participants with mild (n = 7) or moderate (n = 8) hepatic impairment or normal hepatic function (n = 8) received a single oral 100-mg dersimelagon dose. Participants with mild (n = 8), moderate (n = 8), or severe (n = 8) renal impairment or normal renal function (n = 8) received a single 300-mg dose. Systemic exposure to dersimelagon was comparable with mild hepatic impairment but higher with moderate hepatic impairment (maximum observed plasma concentration, 1.56-fold higher; area under the plasma concentration-time curve from time 0 extrapolated to infinity, 1.70-fold higher) compared with normal hepatic function. Maximum observed plasma concentration and area under the plasma concentration-time curve from time 0 extrapolated to infinity were similar with moderate renal impairment but higher with mild (1.86- and 1.87-fold higher, respectively) and severe (1.17- and 1.45-fold higher, respectively) renal impairment versus normal renal function. Dersimelagon was generally well tolerated.