High sense of purpose in life, a fundamental domain of eudaimonic well-being, has been consistently associated with lower risk for various obesity-related chronic diseases. Although this psychological feature correlates with some health behaviors as potential mediators, its association with healthy eating remains less explored. In addition, studies of these psycho-behavioral and health relationships in the South American population are lacking. This research sought to assess: (1) the cross-sectional association between self-reported purpose in life and overall healthy eating patterns, and (2) healthy food intake as a potential mediator of the inverse relationship between purpose in life and waist circumference. Data collected of 2060 US adults from the MIDUS study (5 ± 12 years, 55% women, mostly white people, and 42.5% obese) and 223 Chilean adults from the CHILEMED study (46.6 ± 9 years, 58.3% women, and 71.3% obese) were used. Anthropometric and sociodemographic variables were collected. Sense of purpose was assessed using the purpose in life subscale of the Ryff’s psychological well-being questionnaire. Diet quality was evaluated using healthy eating or low-fat diet indexes, according to extant food intake data in each cohort. The relationship between these variables was estimated by bivariate and multivariate linear regressions with appropriate adjustments. To establish whether a better diet quality could mediate a link of purpose in life and improved nutritional status (assessed by waist circumference), the association between these three variables was tested by bootstrapping-based mediation analysis. Our results show significant associations of sense of purpose with healthy eating and low-fat dietary patterns in both US and Chilean cohorts, respectively, even after adjusting for sociodemographic variables. According to the mediation analysis, the relationship between sense of purpose and waist circumference, as an indicator of abdominal obesity, appears to be partially mediated by healthier food intake in both samples. In conclusion, our findings suggest a plausible mechanism underlying the favorable impact of this well-being dimension on physical health. Given its protective effects, interventions aimed at increasing purpose in life may facilitate adherence to better dietary patterns, which, in turn, will reduce the risk for obesity-related chronic diseases.