Cyclic peptide natural products (NPs) from the soil dwelling Actinomycetota are a bountiful source of bioactive molecules, including medicines, agricultural products, and chemical tools to study biological processes. Additionally, the biosynthetic enzymes that produce them perform unique chemistries and are excellent starting points for biocatalysts. Unfortunately, many biosynthetic gene clusters (BGCs, clusters of genes that encode for the enzymes that produce NPs) are cryptic. Accessing cyclic peptide NPs from these cryptic BGCs is quite challenging, thus slowing the discovery of novel bioactive cyclic peptides that can serve as leads for medicines and agricultural products. Herein, we are using bioinformatics predictions followed by direct chemical synthesis to access NP-inspired cyclic peptides from cryptic BGCs. These peptides have been screened for a variety of activities, leading to novel antibiotic and antiamoebic leads. Additionally, we are discovering and utilizing the biosynthetic enzymes to access otherwise challenging to access cyclic peptides. Overall, these approaches enable us to access to cyclic peptides that are otherwise inaccessible, thus helping to expand the medicinal and agricultural pipelines.