<p>Cancer poses a major global health challenge, driving the continuous search for innovative treatment strategies. In that context, natural products have gained significant attention due to their recognized cytotoxic efficacy against diverse human cancer lineages. <i>Morchella</i> species, commonly known as morel mushrooms, stand out for their historical medicinal applications and diverse bioactive compounds. This review explores the therapeutic potential of key <i>Morchella</i> species, including <i>M. esculenta, M. pulchella, M. conica, M. deliciosa, M. importuna, M. elata, M. angusticeps,</i> and <i>M. sextelata</i>, in the context of cancer treatment. These species contain bioactive compounds that exhibit LC50 values as low as 0.02&#xa0;mg/mL, effectively targeting molecular pathways like p53 and NRF2. These mushrooms are rich in bioactive compounds, such as polysaccharides, phenolics, alkaloids, and secondary metabolites, which exhibit promising anticancer properties. Key mechanisms of action include inducing apoptosis in cancer cells, inhibiting tumour growth and metastasis, modulating the immune system, and reducing oxidative stress through antioxidant effects. <i>Morchella</i> compounds show potential for synergistic use with existing chemotherapy and radiotherapy treatments, opening new avenues for integrative cancer therapies. Future research should focus on elucidating molecular pathways, optimizing formulations, and leveraging biotechnological advancements to maximize the clinical potential of <i>Morchella</i> species. This review underscores the importance of natural products in developing novel, effective cancer therapies and highlights the urgent need for further investigation.</p> Graphical abstract <p></p>