Calcium hydroxide (Ca(OH)NPs), calcium titanate (CaTiONPs) and yttrium oxide (YONPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic effects. However, there are very limited studies available on their genotoxic effects. Hence, this was done to investigate the effects of multiple administration of Ca(OH)NPs, CaTiONPs or/and YONPs on genomic DNA stability, mitochondrial membrane potential integrity and inflammation induction in mouse brain tissues. Mice were orally administered Ca(OH)NPs, CaTiONPs or/and YONPs at a dose level of 50 mg/kg b.w three times a week for 2 weeks. Genomic DNA integrity was studied using Comet assay and the level of reactive oxygen species (ROS) within brain cells was analyzed using 2,7 dichlorofluorescein diacetate dye. The expression level of Presenilin-1, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) genes and the integrity of the mitochondrial membrane potential were also detected. Oral administration of Ca(OH)NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiONPs administration while administration of YONPs did not cause any remarkable change in the integrity of genomic DNA and mitochondrial membrane potential. Highest ROS generation and upregulation of presenilin-1, TNF-α and IL-6 genes were also observed within the brain cells of mice administrated Ca(OH)NPs but YONPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiONPs alone slightly increased ROS generation and the expression level of TNF-α and IL-6 genes. Moreover, no remarkable changes in the integrity of genomic DNA and mitochondrial DNA potential, ROS level and the expression level of presenilin-1, TNF-α and IL-6 genes were noticed after simultaneous coadministration of YONPs with Ca(OH)NPs and CaTiONPs. Coadministration of YONPs with Ca(OH)NPs and CaTiONPs mitigated Ca(OH)NPs and CaTiONPs induced ROS generation, genomic DNA damage and inflammation along with restoring the integrity of mitochondrial membrane potential through YONPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using YONPs to alleviate Ca(OH)NPs and CaTiONPs induced genotoxic effects.