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Background: Recently, more evidence has been presented regarding the role of behavioral activation/inhibition systems as predictors of substance use disorders. In fact, these systems are regarded as potentially important factors in the development of this complex psychiatric problem. Objectives: This study aimed to determine how behavioral activation/inhibition systems, namely behavioral activation, behavioral inhibition, and fight-flight freezing systems, affect substance abuse in bipolar patients. Methods: A total of 79 patients with bipolar disorder were selected among hospitalized patients in the psychiatric ward of Kamkar-Arabnia Hospital in Qom, Iran. The participants completed the Gray-Wilson personality questionnaire, Hamilton Rating Scale for Depression, Mood Disorder Questionnaire, and a sociodemographic questionnaire. Results: Behavioral activation and behavioral inhibition systems emerged as significant predictors of substance abuse in bipolar patients (χ2 = 52.511; df = 3; P < 0.0005). Gender and type of bipolar disorder (I or II) showed no significant association with the scores of behavioral activation, behavioral inhibition, or fight-flight freezing systems. Also, the behavioral inhibition system scores could predict manic mood (χ2 = 7.067; df = 3; P < 0.070). Conclusions: The findings of the current study provide further evidence regarding the role of behavioral activation and inhibition systems as predictors of substance abuse in bipolar patients.