BACKGROUND: We developed My Kidneys & Me (MK&M), a digital health intervention (DHI) that delivers specialist health and lifestyle education, to improve self-management in people with chronic kidney disease (CKD). OBJECTIVE: We aimed to explore the uptake and usability of MK&M alongside patient experiences of using MK&M. METHODS: Adult patients with CKD stages 3-4 were recruited from 26 hospital kidney services in England. Overall, 420 participants were randomized 2:1 to the intervention (MK&M) or control (usual care) group. Uptake and usage data were collected from the MK&M program. Perceived usefulness of the MK&M sessions and features were collected via web-based surveys (scores were rated out of 10, where 0="not useful at all" and 10="very useful"). Qualitative (semistructured and think-aloud) interviews were used to explore participants' experiences of using and engaging with MK&M. Usage metrics were assessed using descriptive and frequency analyses. Qualitative data were analyzed using thematic analysis. RESULTS: Overall, 280 participants were randomized to receive the MK&M intervention (age: mean 60.8, SD 12.8 y; n=161, 57.5% male; eGFR: mean 38.9, SD 18.5 mL/min/1.73 m). Of those, 225 (80.3%) participants activated and used their MK&M account. The median number of log-ins per person was 10.0 (IQR 4.0-28.0). The median time per log-in was 12 (IQR 7-25) minutes. "The kidneys" was the most accessed session (152/225, 67.6%). The educational sessions were the most valued and engaging content, while health and symptom trackers were the least used features. All sessions received scores ≥7 out of 10 for perceived usefulness, with "Kidney disease and general health" considered most useful (score=8.7/10). Goal setting for health behaviors was considered the most useful tracker (score=8.5/10) and symptoms the least (score=6.7/10). Overall, 33 participants were interviewed (n=6, 18% think-aloud; n=27, 81% semistructured). Themes relating to use, usability, and engagement with MK&M were identified. MK&M was well-received, with participants reporting that the user interface was easy to use, with clear and logical navigation and appropriate presentation of information. Learning sessions were more widely accessed and used than the action ("How to...") sessions, with participants highlighting not having enough time to engage with all the MK&M content during the study period. MK&M users had positive experiences of using the program; however, there was ambivalence regarding content and features, which could be explained by personal preference rather than usability issues. Participants had a desire for continued learning and perceived the relevance of MK&M to be greater with time and disease progression. CONCLUSIONS: The MK&M DHI was well-received and used by the participants. Our findings show that a wide range of people with CKD, including older adults, are capable and willing to use DHIs for kidney health. Identification of real-life use and usability issues will help refine MK&M to improve the content and delivery for clinical implementation.