Stroke is a multifactorial disease contributing to significant noncommunicable disease burden in developing countries. Risk of stroke is largely a consequence of morbidities of diabetes, obesity, hypertension, and heart diseases. Incidence of stroke is directly proportional to body mass index. Adipose tissue stores energy as well as acts as an active endocrine organ, which secretes numerous humoral factors. Adiponectin and leptin are the commonest adipocytokines and have been invariably linked to the development of coronary heart disease and may be involved in the underlying biological mechanism of stroke. Leptin and adiponectin mediate proatherogenic and antiatherogenic responses, respectively, and hence, determining the plasma or serum levels of leptin and adiponectin alone or in combination may act as a novel prognostic biomarker for inflammation and atherosclerosis in stroke. This review addresses leptin- and adiponectin-mediated inflammatory mechanism in ischemic stroke and their potential as therapeutic targets.