This study evaluated the psychometric feature of the Persian version of the Fatigue Scale for Motor and Cognitive Functions (P-FSMC) in Iranian People with Multiple Sclerosis (PwMS). In this cross-sectional study, 303 PwMS and 102 healthy controls participated. Structural validity was explored using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Construct validity was determined through correlations of P-FSMC with the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS), besides expected differences in P-FSMC scores and by examining score variations based on disability and depression levels. Fatigue discrimination and diagnostic accuracy between PwMS and healthy controls were evaluated. The P-FSMC demonstrated excellent test-retest reliability and high internal consistency. EFA revealed two factors explaining 70.08% of the variance, with good fit model. The P-FSMC showed moderate to high correlations with FSS and FIS and distinguished different levels of disability and depression. The total score discriminated fatigue with 86.7% accuracy, 84.5% sensitivity, and 93.1% specificity. Cut-off scores for mild, moderate, and severe fatigue severity were ≥46, ≥56, and ≥66, respectively, with high sensitivity (81.52-91.42%) and specificity (80.02-99.01%). The P-FSMC is a reliable and valid questionnaire for assessing fatigue in Iranian PwMS.