Oxidative stress is the main pathophysiological mechanism involved in the development of stroke. Severe DNA damage induced by oxidative stress or apoptotic stimuli activates poly (ADP-ribose) polymerase (PARP), causing a rapid depletion of nuclear NAD pools, cellular energy, and thiols. The biochemical activity of nicotinamide in the body is based on its conversion into NAD. Nicotinamide and its structural analogues possess a weak inhibitory effect on PARP. Nicotinamide exerts its neuroprotective effects by increasing NAD synthesis and ATP production indirectly and inhibiting PARP directly. By inhibiting PARP, membrane phosphatidylserine exposure and DNA fragmentation, nicotinamide can prevent brain necrosis and apoptosis effectively. Administration of nicotinamide at an early stage of stroke provides a new means to rescue the still viable but injured nerve cells within the ischemic and limit areas.