Strokes are the second leading cause of death and the leading cause of long-term disability, globally1. Yet, despite the significant burden strokes represent, no broadly applicable treatments are available. The current methods of treating stroke rely upon distinguishing the type of stroke a patient is experiencing, and must be applied within a certain timeframe2,3. Recently, however, the venom-derived peptide Hi1a has been shown to potentially broaden this therapeutic window by reducing the size of the peri-infarct zone in the brain during a stroke by up to 80% via inhibition of the acid-sensing ion channel 1a (ASIC1a)4. However, this peptide is composed of 87-residues that form two knottin motifs joined together by a short linker4. As a result, it is too large to passively transverse through the blood-brain barrier during the crucial first hours after stroke onset. Additionally, the multiple knottin motifs make it difficult to work with when exploring different delivery methods. Therefore, in order to identify smaller, simpler peptides that replicate this potent inhibitory effect on ASIC1a, we investigated a peptide drug discovery technique known as, Random nonstandard Peptide Integrated Discovery (RaPID). Using RaPID, a library of small, cyclic peptides with high affinity for ASIC1a was generated. Within this library, the most abundant peptides were observed to share a motif with Hi1a that is essential for its potent inhibitory effect. Subsequently, when these peptides were tested, many were found to have low nanomolar potency on ASIC1a. Therefore, these small peptides successful replicate the potency of Hi1a and represent strong candidates for the development of neuroprotective therapeutics for stroke.