We investigated some effects of water pipe smoke (WPS) exposure (30 min/day, for 30 days) in male mice, and the possible ameliorative of gum acacia (GA) coadministration thereon. Controls were exposed to air‐only (AE). Twenty‐four hours post last exposure, the levels of some plasma reproductive hormones, biochemical markers of inflammation, oxidative and nitrosative stress and testicular histopathology were assessed. The concentration of cotinine, the predominant metabolite of nicotine, was also measured in urine. WPS exposure induced a significant decreases in testosterone, estradiol, luteinizing hormone, and androgen binding protein. Inhibin B concentration was significantly increased. Plasma alkaline phosphatase, lipopolysaccharide binding protein, uric acid, and lactate dehydrogenase were all significantly increased following WPS exposure. In testicular homogenate, NF‐κB p65, Nrf2, interleukin‐1β, interleukin‐6, tumor necrosis factor –α, and transforming growth factor‐β1 were all significantly elevated after WPS exposure. WPS exposure decreased nitrite and total nitrite, glutathione reductase activity, and increased lipid peroxidation, cytochrome C, and 8‐Oxo‐2′‐deoxyguanosine. Histopathologically, there was slight reduction in the diameter of the seminiferous tubules with disorganized spermatogenesis. Cotinine concentration was significantly increased in the WPS‐exposed group compared with the control group. GA co‐administration mitigated the adverse actions of WPS measured. We conclude that daily exposure to WPS at the above dose induced damaging effects to the reproductive system in male mice, and that GA co‐administration mitigated the adverse actions of WPS measured.Support or Funding InformationSupported by a joint grant from Sultan Qaboos University and United Arab Emirates University (CL/SQU ‐ UAEU/18/01).