The rate of Type 2 diabetes mellitus (T2DM) among Mexican American individuals is 16.3%, about twice that of non-Hispanic White individuals. While a number of education approaches have been developed and shown to improve diabetes self-management behaviors and glycemic control for Spanish-speaking Latinx patients with T2DM, there is little research to guide health practitioners regarding which interventions to apply and when so that resources are used efficiently, and treatment outcomes are maximized. This study aimed to describe an adaptive intervention that integrates community mental health workers, diabetes nurse educators, family members, and patients as partners in care while promoting diabetes self-management for Mexican American individuals with T2DM. The project incorporates four evidence-based, culturally tailored treatments to determine what sequence of intervention strategies work most efficiently and for whom. Given the increasing prevalence of T2DM, achieving better control of diabetes and lowering the associated medical complications experienced disproportionally by Mexican American individuals is a public health priority. Funded by the National Institute of Nursing Research (National Institutes of Health grant R01 NR015809), this project used a sequential multiple assignment randomized trial and included 330 Spanish-speaking Latinx patients with T2DM. In the first phase of the study, subjects were randomly assigned to an evidence-based diabetes self-management educational program called Tomando Control delivered in a group format for 6, biweekly 1.5-hour sessions, led either by a community health worker or a diabetes nurse educator. In the second phase of the study, those subjects who did not improve their diabetes self-management behaviors were rerandomized to receive either an augmented version of Tomando Control or a multifamily group treatment focused on problem-solving. The primary outcome measure was the "Summary of Diabetes Self-Care Activities." Evaluations were made at baseline and at 3, 6, and 12 months. This study was funded in June 2016 for a period of 5 years. Institutional review board approval was obtained in November 2016. Between March 2017 and September 2020, a total of 330 patients were recruited from the outpatient primary care clinics of Olive View-UCLA Medical Center, with a brief hiatus between May 2020 and July 2020 due to COVID-19 restrictions. The study interventions were completed in December 2020. Data collection began in March 2017 and was completed in December 2021. Data analysis is expected to be completed in Spring 2023, and results will be published in Fall 2023. The results of this trial should help practitioners in selecting the optimal approach for improving diabetes self-management in Spanish-speaking, Latinx patients with T2DM. ClinicalTrials.gov NCT03092063; https://clinicaltrials.gov/ct2/show/NCT03092063. DERR1-10.2196/44793.