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Background: Metabolic syndrome (MetS) increases risk for morbidity and premature mortality. Blood pressure, waist circumference, and fasting triglycerides (TG), blood glucose (BG), and high-density lipoprotein cholesterol (HDL) are factors for determining MetS. The Simple Method for Quantifying Metabolic Syndrome (siMS) score and risk score estimate risk of MetS. The purpose for this study was to exam the relationship of animal-based (ABP) and plant-based protein (PLP) with MetS as estimated by siMS score and risk score. Physical activty is another important consideration in MetS as it can reduce blood pressure, waist circumference and blood glucose, and affect blood lipid and lipoprotein concentrations., Methods: A cross-sectional study examined whether physical activity (PA) level and dietary protein source (i.e., animal- or plant-based) among young (18-24 years) and middle-aged (45-60 years) females were associated with siMS score and siMS risk score. Average time spent in sedentary, light, and moderate-to-vigorous PA (MVPA; min/wk), steps (steps/day), energy intake (kcal/day), percent dietary protein to total energy intake, ABP and PLP dietary intake, and ABP:PLP ratio (g/day) were included in the analysis. Volunteers were recruited from North Dakota and Minnesota from 2017 to 2019., Results: Eighty-one female participants (mean ± SD; young, n = 38, 20.4 ± 1.7 years, middle-aged, 52.5 ± 4.8 years) were included in the independent t -tests used to examine group differences in age, body mass index, HDL, BG, TG, systolic blood pressure, waist circumference, energy intake, energy intake percentage of total carbohydrates, fat, protein, ABP, and PLP, ABP:PLP, siMS score, and siMS risk score. Stepwise linear regressions were used to evaluate whether PA level and dietary protein source were predictors of siMS score and siMS risk score among young and middle-aged adult females. There was an inverse relationship between PLP intake and siMS score. The model explained 6.9% of the variance in siMS risk score (F 1, 80  = 5.93). Plant-based protein intake was inversely related to siMS risk score while light PA was positively associated with siMS risk score. The model explained 16% of the variance in siMS risk score (F 1, 80  = 7.53). Animal-based dietary protein intake did not impact siMS score ( p  = 0.180) and siMS risk score ( p  = 0.283)., Conclusions: Plant-based protein intake was associated with a lower risk of MetS via siMS scores, while ABP was not associated. Given the nature of the cross-sectional design of this study, no causal relationship can be determined, but longitudinal studies or randomized control trials to confirm the results from this study are needed in the future., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)