The gut barrier, comprising the microbiota and their products, mucus layers, host-derived antimicrobial compounds [e.g., host defense peptides (HDP), IgA], epithelium, and underlying immune tissues, performs the essential function of preventing the passage of harmful microorganisms and substances into the body, while enabling the acquisition of dietary nutrients. Antibiotic growth promoters (AGP) are widely accepted as the “gold standard” of performance-enhancing feed additives, which had become integral and valuable components of modern, efficient animal production, but are now being phased out in many parts of the world. This review, therefore, examines the reported effects of AGP on the key components of gut barrier function, particularly where corresponding (positive) growth performance data were provided to indicate that any changes were beneficial, and some important trends do emerge. Certain bacterial families (e.g., Lachnospiraceae), genera (e.g., Faecalibacterium, Propionibacterium, and Ruminococcus), or species (e.g., F. prausnitzii, B. fragilis, and some Lactobacillus spp.) have been reported to increase with AGP use, are associated with improved growth performance, and show benefit across species, which may be related to their production of short-chain fatty acids (SCFA). Various studies have investigated the effects of AGP on mucus-related parameters (e.g., goblet cell size, density, and mucin mRNA expression) but these do not always seem to correlate well with the actual physical characteristics of the mucus layer(s). Surprisingly, there are little data relating to HDP or IgA, even though they have recognized benefits. There are clear AGP benefits on epithelial structure and function (e.g., nutrient digestibility), and these may (currently) provide the most reliable indicators of the efficacy of growth promoters. Data investigating effects on gut immune parameters (e.g., cell populations, cytokines, and chemokines), with corresponding growth performance, are limited and require further detailed interrogation. This review highlights both important observations related to the effects of AGP on key gut barrier components, with associated growth performance, and areas that require further investigation, thus providing an informative basis for assessing the potential of AGP alternatives.