Brain is the central organ in human body, that is working 24hr/7days even before we leave our mother`s womb. None surprising that care should be paid for the food consumed that consequently affecting brain environment, neurotransmitters as well as oxidative state. Carmoisine (Car) and sunset yellow (SY) are synthetic food additives extensively utilized during food processing and subsequently affecting brain health. The apoptotic effect underling the behavioral changes after oral consumption of either Car or SY remains not fully understudied. Respective biochemical and molecular biological parameters by means of one fifty adult male mice were conducted. The study extended for 3 months on 5 different groups with ten mice each; Group 1 was utilized as the control group, group 2 was treated with the acceptable daily intake (ADI) of SY (30 mg/kg BW), group 3 was treated with 10x ADI of SY, group 4 was treated with ADI of Car (4 mg/kg BW) and group 5 was administered 10x ADI of Car; all doses were given orally via gastric lavage. Exposure to higher doses of either SY or Car significantly altered the biochemical parameters; decreased both serotonin and dopamine levels and total antioxidant capacity as well. However, increased the lipid peroxidation marker malonaldehyde (MDA), upregulated the mRNA expression of the pro-apoptotic genes (Fas, Fas-L, Bax and casp3) and down regulated the transcriptional level of the anti-apoptotic gene Bcl2.Moreover upregulated both miR-140 and miR-34a expression levels and consequently down-regulated their target genes NRF-2 and SIRT-1, respectively.  So, we can conclude that excessive oral administration of either Car or SY has apoptotic effect and care should be paid with their usage.