Cephalopods exhibit an extensive range of secretions, including ink, mucus and venom. Sepiadariidae, one family of benthic bobtail squids, possess specialised systems of secretion, secreting a viscous slime from their underside. It is believed that these secretions are involved in defending the species, and exhibit unique biochemical and biophysical properties including dramatic volume expansion, adhesion, and antimicrobial defence. In order to further understand the mechanisms behind the secretion of the slime and the proteins involved, six tissues from four individuals of a species of Sepiadariidae, the striped pyjama squid (Sepioloidea lineolata), underwent label-free quantitation. The proteomic results were combined with a de novo transcriptome and analysed using computational bioinformatics methods, including a proteogenomic pipeline developed in Galaxy. Twenty-eight highly differentially expressed proteins were identified within the slime of S. lineolata, with peptidases and proteases being the most prominent. This was further evidenced by the highly differentially expressed enzymes involved in the post-translational modifications of neuropeptides. While none of the proteins commonly expressed through these pathways were identified (catechloamines and insulin among others), it is possible the novel, short and secreted proteins that were highly differentially expressed, are unclassified neuropeptides. These identified proteases and potential neuropeptides may have further implications for biomimetics within the design of new pharmaceuticals, antimicrobials and antifungals. While traditionally quantitative proteomics is not used to analyse complete proteomes on non-model organisms, our work illustrates that the combination of de novo assembled transcriptomes and comprehensive bioinformatic analysis can provide rapid and informative investigation into species, which have high potential for biological applications without the need for a full genome. Our work incorporates the first label-free quantification analysis of a cephalopod secretion and the first proteomic analysis of the tissues from Sepiadariidae.