Unconjugated hyperbilirubinemia in adolescents with chronic inflammatory disorders may suggest hemolysis, hepatocellular injury, or immune-mediated hepatobiliary disease. In patients on biologic therapy, distinguishing benign hereditary conditions from drug-related adverse effects is crucial. We describe evaluation of mild scleral icterus in a 16-year-old with ulcerative colitis.A 16-year-old female with ulcerative colitis maintained on anti-TNF therapy presented for routine follow-up. Mild scleral icterus was noted. Laboratory tests revealed isolated elevation of total bilirubin, predominantly unconjugated. Hemoglobin, reticulocyte count, peripheral smear, lactate dehydrogenase, and haptoglobin were normal, excluding hemolysis. Liver enzymes, cholestatic markers, and coagulation parameters were within normal limits. Autoimmune serologies (ANA, AMA, ANCA) were negative, making immune-mediated hepatobiliary disease unlikely. Imaging was not indicated. Persistent isolated unconjugated hyperbilirubinemia with normal liver function prompted suspicion of a hereditary disorder. Genetic testing confirmed a UGT1A1 variant compatible with Gilbert syndrome.Although Gilbert syndrome is common, its recognition in adolescents with inflammatory bowel disease is challenging, as mild icterus may be misinterpreted as drug toxicity. Few pediatric cases highlight diagnostic uncertainty in the context of biologic therapy, making this case clinically relevant.Early bilirubin fractionation and prompt exclusion of hemolysis are essential. Recognizing benign hereditary hyperbilirubinemia avoids unnecessary discontinuation of effective therapy and extensive hepatobiliary investigations.Benign metabolic conditions can mimic adverse drug effects in patients on biologics. A structured diagnostic approach—evaluating hemolysis first, followed by autoimmune and cholestatic markers, and concluding with targeted genetic testing—ensures accurate diagnosis while preserving therapy. Clinical stability and normal hepatic parameters confirmed the benign nature.In adolescents with ulcerative colitis, isolated unconjugated hyperbilirubinemia should raise consideration of Gilbert syndrome. Accurate recognition allows safe continuation of therapy and reinforces the importance of a structured, stepwise diagnostic evaluation.