Chagas disease, caused by the protozoan Trypanosoma cruzi, represents a significant public health challenge, particularly in Latin America’s endemic regions. The limited efficacy and frequent adverse effects of current treatments underscore the need for novel therapeutic options. This research explores marine natural compounds as potential candidates for Chagas disease treatment using virtual screening and in silico evaluation methods. Techniques such as molecular docking, drug-likeness evaluation, and pharmacokinetic analysis were employed to identify promising anti-parasitic compounds. Among the candidates, chandrananimycin A, venezueline A, and dispacamide demonstrated high binding affinities to key targets in T. cruzi alongside favorable docking scores and compliance with essential drug-likeness criteria. Pharmacokinetic profiling further supported their therapeutic potential, revealing desirable properties like effective absorption and minimal toxicity. These findings underscore the promise of marine-derived compounds as a valuable source of new drugs, emphasizing the need for further in vitro and in vivo investigations to elucidate their molecular mechanisms and optimize their development as viable treatments for Chagas disease.