Developing effective carbon-carbon bond forming strategies is one of the central topics for organic chemistry, boosting the development of synthetic methods towards complex molecule preparation. Meanwhile, enzymes, biocatalysts existing in nature, can facilitate a stunning array of cyclization reactions through C–C bond formation, in which these late stage ''decorations'' are essential for inherent bioactivity and pharmaceutical use. In this review, we discuss how iron-containing enzymes catalyze intramolecular C–C bond formations found in natural products. Several of these enzymatic processes serve as foundations in developing chemo-enzymatic strategies in complex molecule synthesis.