Background Increasing number of people globally gives in to indiscriminate consumption of excess alcohol as a coping mechanism to relieve any form of physical or psychological stress. Previously, ethnomedicinal use of Zingiber officinale Roscoe (Ginger) have been shown to exhibit broad range of pharmacological benefits but no data has reported the phytotherapeutic treatment of Zingiber officinale methanol extract (MEZO) on alcohol-use disorder (AUD) and post-traumatic stress disorder (PTSD)-induced oxidative and inflammatory stress relevant to disruption of kidney functions in animal model. Objective To investigate the protective effect of MEZO on kidney-oxidative and inflammatory biomarkers in sub-chronic alcohol exacerbation of PTSD symptoms in mice. Methods Male Swiss mice were administered 30% ethanol for two weeks and thereafter introduced to single prolonged stress to induce AUD and PTSD respectively prior to post-treatment with MEZO and vitamin C. Markers of oxidative stress, inflammatory cytokines, kidney functions, HPA-axis signaling molecules, vasodilator substance, and histopathology of the kidney were evaluated. Results Sub-chronic alcohol intoxication heightened PTSD-induced oxido-inflammatory stress, altered the kidney function indices and HPA-axis, and reduced nitric oxide production, which were ameliorated by the phytotherapeutic treatment with MEZO. Furthermore, severe degeneration and atrophy of renal tubules were observed. Meanwhile, MEZO interventions strongly abated all these effects. Conclusions Herein, the study shows that phytotherapeutic treatment with MEZO prevents the damaging effects of co-exposure to sub-chronic alcohol intoxication and PTSD.