Aim <p>This research aimed to investigate the effect of inspiratory muscle training (IMT) on familial Mediterranean fever (FMF) adolescents’ pulmonary functions, fatigue, aerobic capacity, and quality of life (QoL).</p> Methods <p>The included FMF adolescents in this IMT trial were aged ≥ 13 and 17 years old. FMF adolescents (<i>n</i> = 40) were divided into group A or group B. Every FMF group contained twenty FMF adolescents. Both groups continued to take their prescribed daily pharmacotherapies (colchicine) as usual. Group A followed an 8-week supervised IMT program, which was led by a physiotherapist. The total score of the Pediatric QoL Multidimensional Scale of Fatigue (PQoL-MSF) was assessed. Subscales of PQoL-MSF, such as the general fatigue perception subscale, rest- and sleep-associated fatigue perception subscale, and cognitive fatigue perception subscale, were also assessed. The authors assessed physical and mental summaries of the Child Health Questionnaire. FMF adolescents’ ventilatory functions, such as forced vital capacity (FVC), forceful expiratory volume at first second of FMF adolescents’ exhalation (FEV1), and FEV1/FVC ratio, were estimated. Exercise tolerance in FMF adolescents was assessed using the six-minute walk test. Also, maximal inspiratory pressure – as an indicator for inspiratory muscle strength - was measured.</p> Results <p>The assessed outcomes of group A significantly improved. There were no significant improvements mentioned in the outcomes of group B.</p> Conclusion <p>IMT is a promising retraining tool that can be incorporated in the management of FMF to reduce the deterioration in sufferers’ physical capacity, fatigue, ventilatory functions, and QoL.</p>