The European Rapid Alert System for Food and Feed (RASFF) has shown 1133 notifications for spices and herbs in the last 10 years (2013–2023). The analysis of these notifications indicated that 58,7% (665) of the alerts corresponded to chemical hazards. Mycotoxins corresponding to aflatoxin B1 (90) and ochratoxin A (39) were found in 19.4% of the samples. Due to the presence of these biological hazards in foodstuffs, comprehensive knowledge of their molecular mechanisms of action is required as part of the risk assessment strategy. Aflatoxin B1 (AFB1) is a known potent carcinogen that has been linked to liver cancer in humans and animals. Its toxic effects consist of forming DNA adducts, causing mutations, and interfering with cellular processes. On the other hand, ochratoxin A (OTA) is known to be nephrotoxic, hepatotoxic, carcinogenic, and immunosuppressive in both humans and animals. OTA targets the kidneys and liver, exerting its toxic effects similarly to AFB1, i.e., through DNA damage, oxidative stress, and interference with cellular processes. This communication reviews the molecular mechanism of action underlying the toxicity of AFB1 and OTA found in herbs and spices in Europe, focusing on their biosynthesis, toxicodynamics, interaction with cellular components, and the resulting biochemical pathways leading to adverse health effects. Moreover, it discusses potential strategies for mitigating their presence in herbal products, emphasizing the importance of hazard characterization for effective risk management and regulation.