Abstract <p>Doxorubicin (DOX), a chemotherapeutic medicine, are frequently utilized to treat various malignancies, even though it has well-documented negative side effects. Neurotoxic effect is one of the best known and occurs through several mechanisms including oxidative stress and neuro-inflammation. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, is used in several neurodegenerative disease model because of its neuroprotective effects. The aim of this study was to investigate the effects of DOX on antioxidant and inflammatory markers, behavioral parameters and the possible neuroprotective effect of tDCS stimulation on these effects. To induce neurotoxicity, DOX was administered intraperitoneally (i.p.) at 2.15 mg/kg/day, 1 dose in 3 days, 7 times in total for 3 weeks. tDCS treatment was then applied for 5 consecutive days. Catalase (CAT), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) levels were evaluated. Open field test was used to analyzed to locomotor activity and behavioral changes. The DOX group had neuronal alteration as indicated by the elevation of neuro-inflammation markers (IL-1β, TNF-α, and IL-6) with reduced antioxidant marker (CAT). The tDCS-treated group showed a significant reduction in the inflammation biomarkers, with a significant improvement in the antioxidant marker. DOX administration impaired locomotor activity as well as anxiety behaviors of rats. tDCS have also been shown to be effective in preventing behavioral and locomotor changes; therefore, they may be considered as candidates to reduce toxicity effects in DOX treatments. Our findings reveal the importance of tDCS treatment to attenuate DOX-associated neurotoxicity. Through the modification and decrease of indicators of cellular toxicity and the increase of natural antioxidant enzymes, tDCS demonstrated considerable promise for avoiding DOX-induced neurotoxicity.</p>