MicroRNAs (miRNAs) are regulatory, non-coding RNAs involved in the progression of various diseases including cardiovascular disease, viral infections, and cancer. Their functionality arises after a dedicated processing pathway that includes Dicer-mediated cleavage of their precursor structures, typically recognized by their stem loop. Recent discoveries found that certain pre-miRNAs have an alternative precursor structure called a G-Quadruplex (G4), formed via hydrogen bonding between guanine nucleotides. The G4 is unable to be processed by Dicer, preventing the maturation, and therefore function, of the miRNA. Small molecule ligands can bind to and stabilize either the stem-loop or G4 structure in specific pre-miRNAs, altering the potential of either structure to fold. Identifying ligands capable of stabilizing either structure would enable increased understanding of the regulation of miRNA expression, especially in regards to the various diseases which they are involved with. The research presented here analyzes the efficacy of fluorescence-based assays in determining the effectiveness of binding between numerous small molecule ligands and the stem-loop or G4 structure of fluorescently labeled pre-let-7e and pre-miR-92b. It aims to solidify an effective method to test for binding while also assessing where discrepancies and issues may arise in the experimental procedure.