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The World Health Organization regards betel quid (BQ) as a human carcinogen. The BQ chewers may develop dependence symptoms. Although chewing BQ is common in many Asian countries, BQ is still a “populous orphan” in the field of addictive substance. The current review paper systematically reviews the cognitive neuroscientific studies on BQ chewers to understand the chewing effect on cognitive functions and brain. This review includes 25 studies ranged from 1976 to 2019. According to the subjects and study tools, these studies are categorized into “cognitive functions” and “executive control and reward systems.” The “cognitive functions” session includes alertness, selective attention, short-term memory, and executive control. The “executive control and reward systems” session includes the studies that adopted the magnetic resonance imaging to investigate the possible imbalance between the executive control and reward systems. The current review shows that (1) the alertness studies on BQ chewers are few and inconsistent, (2) chewing BQ can affect spatial attention distribution that facilitates target identification, (3) dependent chewers can bias their attention to BQ cues, (4) dependent chewers may have impaired spatial short-term memory, (5) the behavioral studies on executive control are few and inconsistent, (6) imaging studies, in general, show deteriorated executive control in dependent chewers, but show inconsistent patterns on the reward system. The current review discusses several research limitations for future BQ studies. [ABSTRACT FROM AUTHOR]