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olorectal cancer is a disease pertinent due to its prevalence, with notable presence in populations of developed countries. There are several challenges in conventional pharmacological treatments utilizing chemotherapy that needs to be addressed. The severity of its adverse effects means that this therapy is not optimized in improving the quality of life of the elderly as the target subpopulation that often suffers from colorectal cancer, while there also exists resistance against chemotherapeutic agents that incapacitate their effectiveness. Therefore, this review observed the contemporary literature for the past ten years regarding secondary metabolites sourced from marine-derived fungi and actinobacteria as novel alternatives for cytotoxic agents against colorectal cancer cell lines. There are observed 51 compounds from the last decade explored, in which compounds of varied strengths from the marine fungi genus Aspergillus sp., Penicillium sp., Neosartorya sp., Dichotomomyces sp., Paradendryphiella sp. and Westerdykella sp. as well as the actinobacteria genus Streptomyces sp. and Nocardiopsis sp. are observed. In terms of groupings based on chemicals, categories of chemicals found included peptides (diketopiperazines, other cyclic peptides, lipopeptidyl benzophenones, lipopeptides), alkaloids (indoles, cytochalasans, cytochalasins, and a tyrosine derivative), heterocyclic aromatics (one each for the groups piperazine, pyrazine and furan), bianthrones, anthranillic acid derivatives, ?-amino acid derivatives, and macrolides. Furthermore, regarding marine microorganisms, this study also summarizes and analyzes methods for microbial isolation and cultivation, alongside the separation techniques for their desired metabolites and the cytotoxic assays and analyses performed. From 31 metabolites sourced from the marine fungi and 20 sourced from the marine actinobacteria, evaluated and determined through their respective anticancer potencies in IC50 values, tested against the cell lines HCT116, HT29, HCT15, RKO, Caco2, and SW480. With such method, very strong activities were noted for secondary metabolites sourced from Aspergillus sp., Penicillium sp., Paradendryphiella sp. and the actinobacteria Streptomyces sp. Meanwhile, indole alkaloids and diketopiperazines make up the majority of the compounds, as 9 and 8 metabolites respectively. Higher potencies existing in several compounds from those groups were reasoned through the presence of halogen-based functional groups and sulphide groups in indoles and diketopiperazines, respectively.