The alphaviruses Chikungunya (CHIKV) and Mayaro (MAYV) are responsible for acute febrile illnesses, often accompanied by severe and persistent joint and muscle pain. Due to the lack of specific treatment, research into antivirals against these emerging viruses is seen as an urgent need. Previous studies demonstrated that silymarin exhibits potent antiviral activity against CHIKV and MAYV. Here, we evaluate the effects of silymarin in an animal model of alphavirus-induced arthritis and myositis. For this, BALB/c mice were infected with CHIKV or MAYV in the right hind paw pad. The treated groups received silymarin orally (200 mg/kg/day). Animals were monitored daily for 21 days to assess clinical progression. At 7- and 12-days post-infection (dpi), the animals were euthanized and various tissues collected (liver, spleen, paws, quadriceps, extensor digitorum longus, tibial and soleus muscles) for virological and histopathological analyses. Clinical observation revealed reduced paw edema in silymarin-treated animals. In infected and treated animals, the CHIKV viral load was reduced in the spleen (7 and 12dpi), paw (7dpi), soleus muscle, and liver (12dpi). For MAYV, viral load decreased in the spleen (7 and 12dpi), liver, quadriceps, soleus muscle (7dpi), and paw (12dpi). Histological analysis revealed decreased inflammatory infiltrates in the liver, paw, and muscles, as well as reduced number and area of lymphoid nodules in the spleen (12dpi). Additionally, silymarin treatment reduced TNF-α levels in the paw (7 and 12dpi) and quadriceps (12dpi). Then, we concluded that silymarin not only limits viral replication but also mitigates inflammation in various tissues, including muscles and joints, supporting its therapeutic potential against Chikungunya and Mayaro fevers.