BACKGROUND: Despite the growing burden of chronic kidney disease (CKD), disease knowledge and understanding are still lacking, especially in Bangladesh. OBJECTIVE: The aim of this study was to evaluate the outcome of a health education intervention in order to enhance knowledge, health-related quality of life (QOL), and motivation regarding healthy lifestyles among rural and periurban adults suffering from CKD. METHODS: A parallel-group (1:1) randomized controlled trial is ongoing in the Mirzapur subdistrict, Bangladesh, where two groups of patients with CKD are being compared. Patients aged 18 years and over with CKD (stages 1-3) were enrolled in November 2020. Patients were randomly allocated into either the intervention group (n=63) or the control group (n=63). The control group received usual treatment, while the intervention group received health education through a CKD campaign facilitated by a nephrologist and via mHealth (ie, periodic mobile phone calls) from community health workers. Both groups were followed up for a period of 6 months. The primary endpoint is patients' increased knowledge measured using the Chronic Kidney Disease Knowledge Questionnaire. The secondary endpoints are improved QOL measured using the standardized EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire as well as improvements in the levels of blood pressure, BMI, serum creatinine, fasting blood sugar, hemoglobin, cholesterol, high-density lipoprotein cholesterol, triglyceride, serum uric acid, blood urea nitrogen, and albumin to creatinine ratio. RESULTS: Enrollment of participants began in November 2020; the intervention and follow-up were completed in May 2021. We enrolled 126 patients in the study. Patients' mean ages were 57.97 (SD 15.03) years in the control group and 57.32 (SD 14.37) years in the intervention group. There were 45 out of 63 (71%) females in the control group and 38 out of 63 (60%) females in the intervention group. In addition, there were 38 out of 63 (60%) literate patients in the control group and 33 out of 63 (52%) literate patients in the intervention group. CONCLUSIONS: It is expected that a combined approach, incorporating both a CKD campaign and mHealth, for health education may be an effective tool for increasing knowledge and improving QOL among patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04094831; https://clinicaltrials.gov/ct2/show/NCT04094831. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30191.