Simple Summary The aim of this study was to determine the effect of partial and total replacement of protein from genetically modified soybean meal (GM-SBM) with protein from 00-rapeseed meal (00-RSM), alone or in combination with protein from low-tannin faba bean seeds (FB) or low-alkaloid yellow lupine seeds (YL) in grower-finisher diets on nutrient digestibility, nitrogen retention, and utilization, selected blood biochemical parameters and fattening performance of pigs. During two-phase fattening, hybrid Danbred growing-finishing pigs were fed grower diets where 50% of GM-SBM protein was replaced with 00-RSM protein, 00-RSM and FB protein or 00-RSM and YL protein, and finisher diets where 100% of GM-SBM protein was totally replaced with 00-RSM protein, and with 50% 00-RSM and FB protein or YL protein. It was found that GM-SBM protein can be partially (50% in grower diets) and totally (100% in finisher diets) replaced with 00-RSM protein (6%) combined with protein from low-tannin FB seeds (10%/12%) or low-alkaloid YL seeds (6%/7%) in pig diets. The evaluated diets contributed to high nutrient digestibility and N retention and improved fattening performance without compromising the health status of pigs. Abstract The aim of this study was to determine the effect of partial and total replacement of protein from genetically modified soybean meal (GM-SBM) with protein from 00-rapeseed meal (00-RSM), alone or in combination with protein from low-tannin faba bean (Vicia faba L.) seeds (FB) or low-alkaloid yellow lupine (Lupinus luteus L.) seeds (YL) in grower-finisher diets on nutrient digestibility, nitrogen retention and utilization, selected blood biochemical parameters, fattening performance of pigs and carcass quality traits. Two digestibility-balance trials and one feeding trial were performed during two-phase fattening on male hybrid Danbred growing-finishing pigs were divided into four groups. The pigs were fed grower diets where 50% of GM-SBM protein (diet S-c) was replaced with 00-RSM protein (diet R), 00-RSM and FB protein (diet R + FB) or 00-RSM and YL protein (diet R + YL), and finisher diets where 100% of GM-SBM protein (diet S-c) was totally replaced with 00-RSM protein (diet R), and with 00-RSM and FB protein (diet R + FB) or YL protein (diet R + YL) in 50%. It was found that partial (50% in grower diets) and total (100% in finisher diets) replacement of GM-SBM protein with 00-RSM protein combined with FB or YL protein had no adverse effect on nutrient and energy digestibility, N balance, serum of blood carbohydrate and protein metabolism or the biochemical parameters of liver and kidney function. Protein from 00-RSM (6%) and FB seeds (10%/12%) contributed to high daily gains and high feed conversion efficiency. Protein from 00-RSM (6%) and YL seeds (6%/7%) in grower-finisher diets led to a further improvement in fattening performance. The analyzed vegetable protein sources had no negative influence on carcass quality. The results of the present study indicate that 00-RSM protein combined with protein from low-tannin FB or low-alkaloid YL seeds can be valuable high-protein feed ingredients alternative to GM-SBM in pig nutrition.