This Study focuses on the examination of the role of AMPs in two different pathological conditions: namely Alzheimer’s disease (AD) and oral cancer along with two precancerous conditions. Given the inflammatory nature of AD, we aimed the examination of antimicrobial and immunomodulatory peptide (AMP) family in human proteome datasets deposited in the publicly available proteomics repositories. First, a unified, complete human antimicrobial and immunomodulatory peptide database (UDAMP) was created, coupled with the examination of datasets downloaded from publicly available sources containing high-quality proteomics data derived from AD and control groups. Extensive network analysis was used to study the possible implications of AMPs in the pathogenesis of AD. AMPs made up less than 1% of all detected proteins in the brain, but their study could replicate the abnormalities previously identified in AD. Our findings emphasize the significance of the innate immune system and blood clotting in the progression of AD and can provide with new potential therapeutic targets. Saliva is a bodily fluid with great diagnostic potential aiming to help diagnose oral malignancies. Apart from oral squamous cell carcinoma (OSCC), it is critical to examine precancerous conditions such as oral lichen planus (OLP) and leukoplakia (OLK) as well. Our aim was to assess the changes in salivary AMPs in case of patients with OSCC, OLK or OLP. Our research revealed pathways and proteins characteristic to each condition and highlighted the distinct natures of the OLK and OLP. Our study indicates that AMPs constitute a functionally important class of proteins and their analysis can give valuable insights on the pathogenesis of AD, OSCC, OLK and OLP. The examination of AMPs can provide with useful information about the disease and potential biomarkers able to help the diagnosis or the progression of the diseases.