Aflatoxin B1 (AFB1) is acknowledged as a remarkably powerful genotoxic and hepatocarcinogenic substance, posing a significant public health risk. This study examined the capacity of ultrasound nanobubbles containing TAK-242 to alleviate hepatorenal toxicity induced by AFB1 in rats. A total of thirty-two male albino rats were divided into four equal groups: a control group, a group treated with TAK-242-loaded nanobubbles, a group exposed to AFB1, and a group receiving both AFB1 and TAK-242-loaded nanobubbles. The therapeutic intervention involved the administration of 150 μl of nanobubbles twice a day after exposure to AFB1, together with a 15-minute ultrasound session at a frequency of 5 MHz. Following a 14-day duration, evaluations were conducted using biochemical analyses, gene expression investigations, and histological evaluations. Rats that were intoxicated with AFB1 showed decreased levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in their plasma. Additionally, they exhibited increased levels of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, and creatinine. In addition, there was an increase in the expression of toll-like receptor 4 (TLR4) and neutrophil gelatinase-associated lipocalin (NGAL) genes, along with significant histopathological damage to the liver and kidney tissues. The administration of TAK-242-loaded nanobubbles significantly improved these harmful effects, by strengthening the body's antioxidant defenses and decreasing both the biochemical and histopathological changes in the liver and kidney tissues.