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In pigs, high protein diets have been related to post-weaning diarrhoea, which may be due to the production of protein fermentation metabolites that were shown to have harmful effects on the intestinal epithelium in vitro. In this review, we discussed in vivo effects of protein fermentation on the microbial composition and their protein catabolic activity as well as gut and overall health. The reviewed studies applied different dietary protein levels, which was assumed to result in contrasting fermentable protein levels. A general shift to N-utilisation microbial community including potential pathogens was observed, although microbial richness and diversity were not altered in the majority of the studies. Increasing dietary protein levels resulted in higher protein catabolic activity as evidenced by increased concentration of several protein fermentation metabolites like biogenic amines in the digesta of pigs. Moreover, changes in intestinal morphology, permeability and pro-inflammatory cytokine concentrations were observed and diarrhoea incidence was increased. Nevertheless, higher body weight and average daily gain were observed upon increasing dietary protein level. In conclusion, increasing dietary protein resulted in higher proteolytic fermentation, altered microbial community and intestinal physiology. Supplementing diets with fermentable carbohydrates could be a promising strategy to counteract these effects and should be further investigated.