The vegan diet excludes animal-derived product consumption and health advantages had been reported when followed. However, heterogeneous eating habits, food availability, and sociocultural characteristics among regions could lead to different physiological results. The objective of this case-control cross-sectional pilot study was to analyze body composition, daily nutrients consumption, and basic serum biomarkers as a general overview of the health status of Mexican adults with a vegan diet for ≥3 years, randomly paired with omnivores. Body composition was assessed through bioelectric impedance analysis. Eating patterns were evaluated and daily nutrients intake was calculated. A complete blood count, glycated hemoglobin, cobalamin, and creatinine serum concentrations were analyzed. We hypothesized certain nutrient deficits and specific biomarker impairments originated from cultural particularities driving food selection in Mexicans following a plant-based diet. Body composition did not differ among groups. Lower protein, niacin, pantothenic acid, pyridoxine, cobalamin, calciferol, fluoride, iodine, and selenium intake yet greater fiber, folic acid, vitamin E, copper, and molybdenum were observed in the plant-based group when compared with controls. Vegans presented lower cobalamin and creatinine serum concentrations. Hematologic abnormalities were prevalent in vegans. Insufficient consumption of several nutriments was identified in both dietary groups, suggesting that the local diet may be unbalanced, affecting both vegans and non-vegan individuals. However, vegans might present additional deficiencies, especially vitamin B₁₂, with potential repercussions. Clinical and nutritional guidance is required in this particular population to avoid possible health adverse events.