Polyglutamine (polyQ) diseases are a group of hereditary neurodegenerative disorders caused by expansion of unstable polyQ repeats in their associated disease proteins. To date, the pathogenesis of each disease remains poorly understood, and there are no effective treatments. Growing evidence has indicated that, in addition to neurodegeneration, polyQ-expanded proteins can cause a wide array of abnormalities in peripheral tissues. Indeed, polyQ-expanded proteins are ubiquitously expressed throughout the body and can affect the function of both the central nervous system (CNS) and peripheral tissues. The peripheral effects of polyQ disease proteins include muscle wasting and reduced muscle strength in patients or animal models of spinal and bulbar muscular atrophy (SBMA), Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and spinocerebellar ataxia type 17 (SCA17). Since skeletal muscle pathology can reflect disease progression and is more accessible for treatment than neurodegeneration in the CNS, understanding how polyQ disease proteins affect skeletal muscle will help elucidate disease mechanisms and the development of new therapeutics. In this review, we focus on important findings in terms of skeletal muscle pathology in polyQ diseases and also discuss the potential mechanisms underlying the major peripheral effects of polyQ disease proteins, as well as their therapeutic implications.