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Simple Summary: Broiler chicken welfare is under increasing scrutiny due to welfare concerns regarding growth rate and space provided to individual birds (stocking density). Stocking density in broiler production is perceived as a topic of major importance because the producer always wants to raise a higher number of birds in the limited space available to increase profitability. By using the novel approach of nanotechnology, the scientific team made Selenium nanoparticles (SeNPs) and supplemented them along with mannan oligosaccharide (MOS), a prebiotic, in higher stocking density (HSD)-stressed broilers. A 42 day long experiment was conducted and sampling was carried out at the 21st day and 42nd day to assess the possible effects of HSD and supplementation on the growth performance and development of the gastrointestinal tract. They found that supplementing the HSD-stressed broiler diet with SeNP–MOS improved growth performance, feed intake and feed conversion ratio (FCR). The weekly body weight gain and final body weight of market-age HSD-stressed broilers were significantly improved when supplemented with SeNP–MOS. Supplementation with SeNP–MOS in the HSD broilers improved the GIT microarchitecture involved in nutrient absorption. This led to a higher availability of nutrients for skeletal development, such as muscle and bone, and a better survival rate of birds under HSD. The current study investigated the potential of selenium nanoparticles (SeNPs) and mannan-oligosaccharide (MOS) supplementation in ameliorating high stocking density (HSD) stress in broilers. A total of 392 day-old male chicks were divided into seven groups with eight replicates (n = 7): NSD [basal diet (BD) + normal stocking density: 10 bird/m2], HSD [BD + high stocking density: 16 bird/m2], Se–HSD [BD + Selenium (Se) 0.15 mg/kg], MOS–HSD (BD + MOS 5 gm/kg), Se–MOS–HSD (BD + Se 0.15 mg/kg and MOS 5 gm/kg), SeNPs–HSD (BD + SeNPs 0.15 mg/kg) and SeNPs–MOS–HSD (BD + SeNPs 0.15 mg/kg and MOS-5 gm/kg). HSD stress decreased (p < 0.05) weekly body weight and body weight gain and increased (p < 0.05) FCR compared to the NSD group. Supplementation with SeNPs and the SeNPs–MOS combination improved (p < 0.05) the weekly body weight and FCR in HSD-stressed broilers during the 5th and 6th weeks. On day 21, HSD stress decreased (p < 0.05) duodenal villus height (VH) and villus surface area (VSA) and increased (p < 0.05) serum corticosterone and cholesterol compared to the NSD group. Supplementation with the SeNPs–MOS combination increased (p < 0.05) duodenal VH and VH:CD, and jejunal total goblet cell (TGC) density and decreased (p < 0.05) serum corticosterone and cholesterol and ileal intra-epithelial lymphocyte (IEL) density in HSD-stressed broilers. On day 42, HSD stress decreased (p < 0.05) duodenal and jejunal VH, VSA, VH:CD, PCNA positive cell density and TGC density, Ileal VSA and TGC density, and increased (p < 0.05) serum cholesterol and ileal IEL density compared to the NSD group. Supplementation with the SeNPs–MOS combination increased (p < 0.05) spleen and bursa absolute weights, duodenal VH, VSA, VH:CD, PCNA positive cell density and jejunal VH, VH:CD, and decreased (p < 0.05) serum cholesterol and ileal IEL density in HSD-stressed broilers. Our findings signify that HSD is stressful for broilers particularly during the finishing phase. Supplementation with the SeNPs–MOS combination mitigated HSD stress by partially improving the gut microarchitecture, gut barrier function and performance indicators. [ABSTRACT FROM AUTHOR]