Severe and fatal influenza type A (IAV) infections are associated with significant viral replication and damaging hyperinflammatory immune responses in the lung. LAT8881 (is a 16 amino acid synthetic form of the naturally occurring C-terminal fragment of growth hormone (GH). LAT8881 has been previously shown to act independently of the GH receptor to reduce inflammatory damage and promote tissue repair in a rabbit model of arthritis. Additionally, LAT8881 has been investigated in several clinical trials in healthy volunteers and has an established safety record. Considering its effects in improving inflammatory damage in animal models, we investigated the potential of LAT8881 and related compounds as a treatment in a mouse model of severe IAV infection (104 PFU HKx31 H3N2). Daily, intranasal (IN) delivery of synthetic GH fragment LAT8881 (≤ 20mg/kg) from 1 day following IAV infection significantly reduced disease susceptibility and resulted in a dose dependent reduction in infectious viral loads, innate immune cell infiltrates and proinflammatory cytokines in the lungs. The efficacy of LAT8881 IN treatment was comparable to that of daily, oral administration of neuraminidase inhibitor, oseltamivir, however, LAT8881 did not hinder IAV or SARS-CoV-2 replication in vitro, which suggests against a direct antiviral role for the peptide. Intriguingly, similar results are achievable using a small peptide derived from the C-terminus of prolactin, a structural homolog of GH. LAT8881 and similar peptides are potent modulators of influenza disease and are novel candidate therapeutics that limit viral replication and reduce airway hyperinflammation. Furthermore, the demonstrated clinical safety profile of LAT8881 warrants future clinical studies of influenza disease and may facilitate its rapid deployment as a treatment for respiratory virus infections.