This study was aimed at determining the possibility of applying rapeseed cake (RC) and wheat distillers dried grains with solubles (DDGS) in diets for HYPLUS meat-type rabbits (n = 64, aged 35–84 days). Control diet (SC) contained 5% of extracted soybean meal. In RC diet, the soybean meal was replaced by RC, in DG diet – by wheat DDGS, whereas in RC–DG diet – by a mixture of RC and wheat DDGS (2.5% each). The study included production analyses, digestibility-balance experiment and physiological assessment of gut response to experimental factors hence data was collected on daily bodyweight gains, feed intake and slaughter performance, nutrients digestibility, nitrogen retention and gut response. The latter included assessment of parameters describing the small intestinal, cecal, and colonic environment of rabbits (e.g. digesta viscosity, ammonia concentration, bacterial enzymes activity, short-chain fatty acid concentration). The highest productivity results were reported for SC group and the lowest ones for DG group. The RC and RC–DG groups were characterised by intermediate productivity. Dressing percentage and contents of carcass elements did not differ among the groups (except for the hind part). Nutrients digestibility and nitrogen retention were the highest in the SC group and the lowest in DG group. The dietary incorporation of DDGS resulted in undesired responses of the gastrointestinal tract including excessively watery digesta in the small intestine, increased concentration of cecal and colonic ammonia, enhanced activity of potentially harmful bacterial β-glucuronidase in cecal digesta, and increased cecal concentration of putrefactive short-chain fatty acids. These negative effects were not due to RC and RC–DG dietary treatments, apart from decreased dry matter concentration in the small intestine in the RC–DG group. In general, the results of our study demonstrated that 5% rape cake can be successfully incorporated into rabbit dietary regimen as a substitute of dietary soybean meal. Considering that the productivity of rabbits fed 2.5% of DDGS (with 2.5% rape cake) and these receiving 5% rape cake was comparable, optional seems also dietary inclusion of up to 2.5% wheat DDGS The higher content of DDGS (5%) in the diet deteriorated most of the growth parameters of rabbits.