Obesity and Type 2 diabetes (T2D) are globally significant health conditions that are projected to worsen. Obesity results from chronic positive energy balance, and T2D is strongly related to obesity. Results from meta-analyses comparing low- and high-fat dietary approaches show no clear differences in long-term outcomes for weight loss or diabetes, although there is better-quality long-term evidence for low-fat approaches. Across the range of dietary strategies presented weight loss ranges from 0 to 11 kg at 1 year. Discussed are relevant mechanistic signaling pathways for obesity and T2D for both low- and high-fat approaches. A convergence of evidence agrees nutrient-rich, low-energy density plant-based foods promote health for people diagnosed with obesity and/or T2D. All diets appear to have difficulties with long-term adherence. More high-quality research is needed.