Inflammation and sleep disturbances increase the risk of multiple diseases, including cardiovascular disease, type 2 diabetes and dementia. Since diet plays a significant role in inflammatory responses and sleep quality, this study aimed to investigate the association of a plant-based diet index (PDI) with sleep quality and inflammatory markers in overweight and obese women.390 overweight and obese women aged 18-48 years participated in this cross-sectional study. A validated food frequency questionnaire (FFQ) was used to create an overall PDI, healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI). Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI). Higher scores on the PSQI were indicative of poor sleep. Anthropometric measurements and serum concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin 1 beta (IL-1β) and transforming growth factor-beta (TGF-β) were evaluated. Linear regression models were used to determine the association between exposure and outcomes.After taking potential confounders into account, we found a significant inverse association between adherence to hPDI and hs-CRP (β = -0.14, 95% confidence interval [CI]: -0.22,0.06, P = .001) and a significant positive association between uPDI and hs-CRP (β = 0.13, 95% CI: 0.05,0.21, P = .001). Overall, PDI was significantly associated with TGF-β (β = 2.04, 95% CI: 0.54,3.55, P = .008). No association was detected between PDI indices and IL-1β. Higher adherence to uPDI was significantly associated with higher PSQI score (lower sleep quality) (β= 0.20, 95% CI:0.007,0.40, P = .04). A significant positive association was found between TGF-β (β = 0.05, 95% CI:0.005,0.10, P = .03) and hs-CRP (β = 0.32, 95% CI:0.02,0.62, P = .03) with PSQI.Our findings indicated a significant association between adherence to a plant-based diet with inflammation and sleep quality in obese and overweight females. WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Sleep is an essential part of life, and sleep quality has a significant impact on individual well-being and performance. There is a bidirectional relationship between disturbed sleep and elevated levels of inflammatory markers. Diet plays a major part in sleep quality and its related health consequences. Plant-based diets are associated with lower risk of chronic diseases such as coronary artery disease (CAD), type 2 diabetes, obesity and reduced level of inflammation. WHAT DOES THIS ARTICLE ADD?: Adherence to a healthful plant-based diet is associated with lower level of hs-CRP, while adherence to an unhealthful plant-based diet is associated with higher concentrations of hs-CRP. Adherence to an unhealthful plant-based diet is associated with lower sleep quality.