The bioactive natural products of cyanobacteria show great therapeutic promise in the treatment of a number of ailments. Advancement of these compounds into clinical settings is greatly facilitated by knowledge of the molecules' cellular target and mechanism of action. This thesis presents the multidisciplinary examination of the bioactivity and mechanism of action of the cyanobacterial marine natural product honaucin A. Preliminary evidence for the anti-inflammatory activity of honaucin A was observed in in vitro assays. Evaluation of analogues of honaucin A revealed that certain structural features were necessary for this bioactivity. The marine natural product was subsequently shown to exhibit in vivo activity in the Mouse Ear Edema Model. RNA sequencing of was utilized as a method of understanding differences in gene expression of cultured macrophages that result from honaucin A treatment. This analysis led us to hypothesize that honaucin A exerts its bioactivity through activation of the cytoprotective Nrf2 (nuclear erythroid 2-related factor 2)-ARE/EpRE (antioxidant response element/ electrophile response element) signaling pathway. Activation of this pathway by honaucin A in cultured human cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-L-cysteine suggested that honaucin A may have the ability to activate this pathway through covalent interaction with the sulfhydryl residues of the repressor protein Keap1. Screening of a library of marine natural products uncovered eight compounds in addition to honaucin A that activate Nrf2-ARE/EpRE. These molecules, isolated from cyanobacteria and an alga, bear structural similarities to honaucin A. This panel of Nrf2-ARE activators may have applications in the treatment of disorders with inflammatory components including neurodegeneration, cadiovascular diseases, cancer, and obesity