This study aimed to determine the effect of antiretroviral therapy (ART) on glycemia and transaminase levels in HIV-infected patients in Limbe, Cameroon. A total of 200 ART-experienced patients and 30 ART-naive HIV-infected controls were recruited after submitting signed informed consent forms. The blood samples collected were screened for hepatitis B and C, and liver transaminases and random blood sugar (RBS) levels were determined spectrophotometrically. No significant correlation existed between the RBS and transaminase levels with either the duration of ART or the duration since HIV diagnosis. Although both groups of patients appeared to have similar transaminase and RBS levels, after controlling for confounders, patients on ART had significantly higher aspartate aminotransferase levels, significantly lower alanine aminotransferase levels, and slightly (but not significantly) lower glycemia levels (respective mean differences of 14.92 IU/L, P = .00; 11.95 IU/L, P = .00; and 7.60 mg/dL, P = .19). These changes need to be considered in monitoring patients on ART in this setting and other similar settings.