Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) represents a significant contributor to morbidity and mortality globally following stroke events. To date, extensive research has been conducted on vascular dementia (VaD) and its underlying mechanisms. However, the potential influence of endogenous formaldehyde on VaD has garnered considerable attention among researchers. This chapter delineates the role of formaldehyde in stroke, its involvement in protein cross-linking during blood coagulation, and its impact on lipid peroxidation and atherosclerosis. Furthermore, we explore the correlation between formaldehyde-induced cognitive impairment and VaD, along with alterations in endogenous formaldehyde levels among stroke and VaD patients. Additionally, we review the plausible mechanisms through which formaldehyde and formic acid exert effects on stroke and cognitive decline. Hypertension and oxidative stress stimulate the expression of semicarbazide-sensitive amine oxidase (SSAO) in blood vessels, resulting in excessive formaldehyde production. Elevated levels of formaldehyde (or formic acid) may represent a potential risk factor for stroke in patients with hypertension and hyperlipidemia, potentially precipitating the development of VaD. Collectively, the findings from existing research suggest that formaldehyde and formic acid could emerge as biomarkers and viable therapeutic targets for the clinical management of stroke and VaD.