OBJECTIVE: Determine the association of parental health literacy with treatment response among children with nephrotic syndrome. METHODS: This was a cohort study of children aged 1–18 with nephrotic syndrome and their parent. Health literacy was measured using the validated Short Test of Functional Health Literacy in Adults assessing reading comprehension and numeracy. Outcomes included initial relapse-free period, frequently relapsing disease, relapse rate, second-line medication use, and complete remission after therapy. RESULTS: Of 190 parents, 80% had adequate health literacy (score >67 of 100), and higher scores were not correlated with higher education. Almost all achieved perfect numeracy scores (>86%); numeracy was not associated with outcomes. After adjusting for immigration, education, and income, higher reading comprehension scores (tertile 3) compared with lower scores (tertile 1) were significantly associated with lower risk of first relapse (hazard ratio 0.67, 95% confidence interval [CI] 0.48–0.94, P trend = .02), lower odds of frequently relapsing disease (odds ratio [OR] 0.38, 95% CI 0.21–0.70, P trend = .002), lower relapse rate (rate ratio 0.77, 95% CI 0.73–0.80, P trend < .001), and higher odds of complete remission after both initial steroids and cyclophosphamide (OR 2.07, 95% CI 1.36–3.16, P trend = .003; OR 5.97, 95% CI 2.42–14.7, P trend < .001). CONCLUSIONS: Lower parental health literacy, specifically reading comprehension, is associated with higher relapse rates among children with nephrotic syndrome and fewer achieving complete remission. This underscores the importance of assessing and targeting health literacy for chronic management of childhood-onset diseases.