Both cottonseed meal (CSM) and dried distiller's grains with solubles (DDGS) are important plant protein sources for fish. This study investigated the effects of dietary DDGS inclusion to replace different portions of CSM on growth performance, muscle texture, health status as well as myogenic‐related genes expression of juvenile grass carp (initial weight: 5 g). A 60‐d feeding trial was performed by feeding fish with three isonitrogenous and isoenergetic diets containing different levels of DDGS (0, 10.3% and 20.6%). The highest growth and feed efficiency occurred at 20.6% DDGS dietary inclusion. Body condition factor, hepatosomatic index, serum ALT and AST as well as hepatic GSH and T‐SOD all showed a downward trend with increasing dietary inclusion of DDGS (p < .05). Collagen content in raw muscle increased with DDGS inclusion. However, DDGS inclusion decreased muscle texture indices and muscle fibre density, while increased muscle fibre diameter (p < .05). Dietary DDGS inclusions significantly upregulated the expression of fgf6a, myh1, myh2 and myh4 in muscle, while downregulated the expression of myod, myf5, myog, mrf4, mstn1, fgf6b and myh7. Overall, dietary DDGS replacing CSM positively affects growth by regulating gene expression involved in myogenesis and hypertrophy, while depressed antioxidant capacity.