Background: Immune dysregulation is one of the hypotheses brought up to explain autism spectrum disorder (ASD). Interleukine-17A (IL-17A), a proinflammatory cytokine, has been demonstrated to be a major mediator of immune-related neurodevelopmental impairment of social behavior, including ASD. Chrysin (CHN) is a naturally occurring hydroxylated flavonoid with antioxidant, anti-inflammatory, anti-asthmatic, anticancer, cardioprotective, and neuroprotective activities. The current study investigated the effects of CHN against Polyinosinic:polycytidylic acid (Poly (I:C))-induced autism-like behavior by modulating the fetal serotonin and IL-17A levels in fetal and offspring brains in C57BL/6J mice. Methods: Pregnant C57BL/6J mice (n = 6) were randomly selected. After the confirmation of pregnancy, female mice were divided into two different experimental groups (n = 3 female/group = 4–8 littermates/group). The pups were randomly divided into 5 experimental groups, namely, control (group I), Poly (I:C) (group II), CHN25 (group III) & CHN50 (group IV), and fluoxetine (group V). Group I and II pregnant mice were pre-treated orally with saline for 12 consecutive days (Estrus Day 0.5 (E0.5) to E12.5) and then challenged with saline (group I) and Poly (I:C) [20 mg/kg Body Weight (BW)] (group II) intraperitoneally on the 12th day (E12.5). Group III, IV & V pregnant mice were administered orally with CHN (25 mg/kg & 50 mg/kg BW) and fluoxetine (10 mg/kg, BW), respectively, for 12 consecutive days (E0.5 to E12.5) and then challenged with Poly (I:C) (20 mg/kg BW) intraperitoneally on 12th day (E12.5). In one set of studies, 1 pregnant mouse from each group was sacrificed after 4 h of Poly (I:C) injection to measure the fetal 5-Hydroxytrptophane (5-HT) and IL-17A levels in fetal brains using enzyme-linked immunosorbent assay (ELISA) kits. In the second set of experiments, the remaining pregnant mice were allowed to deliver the pups. Offspring were subjected to different behavior tests, including marble burying test (MBT), rotarod test, social interaction test (SIT) and sucrose preference test (SPT) at the age of 6, 7 and 12 weeks to investigate the autistic-like behaviors and associated symptoms. Following behavioral studies, the mice were sacrificed to isolate the prefrontal cortex (PFC), hippocampus (HC) and amygdala (AMG) tissues to measure the IL-17A levels through an ELISA kit. Results: The findings of the present study demonstrated that Poly (I:C) administration to pregnant mice resulted in maternal immune activation (MIA), as evidenced by the significant increase in IL-17A (p < 0.05) and decrease in 5-HT levels (p < 0.001) in fetal brains. Pre-treatment of CHN and fluoxetine altered the fetal 5-HT and IL-17A levels significantly (p < 0.001). Offspring of Poly (I:C) injected pregnant mice showed autistic-like behaviors and associated symptoms as evidenced by an increased number of marbles buried in MBT and decreased fall in time in the Rotarod test, sucrose preference in SPT, and social preference in SIT significantly (p < 0.001) which were ameliorated by the chronic pre-treatment of CHN (both the dosages i.e., 25 & 50 mg) and fluoxetine significantly (p < 0.001). Further, results showed the significant elevation of IL-17A levels in PFC (p < 0.001), HC (p < 0.001) and AMG (p < 0.05) of offspring of Poly (I:C) injected pregnant mice, which were attenuated significantly by the chronic pre-treatment of CHN (both the dosage i.e., 25 & 50 mg) and fluoxetine (p < 0.001). Conclusion: Findings of the study demonstrated that chronic pre-treatment of CHN attenuated autistic-like behavior by altering fetal 5-HT and IL-17A in fetal brain, PFC, HC, and AMG of offspring of MIA pregnant C57BL/6J mice. However, further investigation is required to establish the therapeutic applicability of CHN in ASD.