Post-traumatic stress disorder (PTSD) and metabolic syndrome (MetS) are often comorbidities and share neurobiological and clinical features. In particular, the results of meta-analyses indicate a higher prevalence of MetS in patients with PTSD compared to the general population. At the same time, PTSD is also a known risk factor for MetS. The involvement of common pathogenetic mechanisms characteristic of both conditions partially explains this coincidence. Insufficient intake and deficiency of certain biofactors, especially micronutrients (vitamins and essential minerals), are associated with an increased risk of MetS, type 2 diabetes mellitus, and cardiovascular diseases, and maintaining their physiological content in the body reduces this risk. Taking nutritional supplements with certain biofactors may help as an adjunct to conventional therapy to prevent and treat PTSD and, more often than not, MetS at the same time. This is because both conditions are linked to deficiencies in a number of biofactors. This review aims to discuss the role of several biofactors, including α-lipoic acid, vitamin B1/benfotiamine, L-carnitine and acetyl-L-carnitine, ω-3 polyunsaturated fatty acids, quercetin, magnesium, vitamins D and E, polyphenols, in the prevention and treatment of PTSD and MetS comorbidity, as well as to analyze new trends and future research directions. We conducted the search in databases such as Scopus, Science Direct (from Elsevier), PubMed, and MEDLINE. The keywords used were “post-traumatic stress disorder”, “metabolic syndrome”, and “biofactors”. We manually searched the bibliography of publications to identify research results that were not found during the online search.