Plant-based diets (PBD) have been found to be environmentally sustainable as well as beneficial for health. Observational research showed that higher plant-based diet quality improves well-being in adult women, however this is unclear for older adults. This association may be due to anti-inflammatory properties of PBD. Older adults, often suffering from chronic inflammation, may therefore profit from a more PBD. Therefore, we investigated the relation between PBD and well-being in older adults of both genders and tested whether the effects are influenced by circulating high-senstivity C-reactive protein (hsCRP) levels. We used the data of the population-based Lifelines Cohort Study (n=6,635, mean age=65.2 years) and a subsample in which hsCRP was measured (n=2,251, mean age=65.2 years). We applied a plant-based diet index measuring adherence to a healthful (hPDI) and an unhealthful (uPDI) plant-based diet based on food frequency questionnaires. The RAND-36 questionnaire was applied as measure of quality of life, from which we derived physical (PCS) and mental component scores (MCS). Older adults with the highest adherence to a healthful plant-based diet had respectively 14% and 12% greater odds for high physical well-being and mental well-being. Meanwhile, higher adherence to uPDI was associated with respectively 19% and 14% lower odds for high physical and mental well-being. We observed an additive but no mediating effect of hsCRP on the association between plant-based diets and well-being. We conclude that in older men and women, adherence to a healthful plant-based diet and circulating levels of inflammation are independently associated with physical and mental well-being.