Muramyl dipeptide (MDP) - an essential bacterial cell wall component - is recognized by our immune system as pathogen-associated molecular pattern (PAMP) which results in immune responses with adverse toxic effects. In order to harness the beneficial properties from the pro-inflammatory characteristics of the bacterial cell wall motif, MDP was strategically re-designed while conserving the L-D configurations of the dipeptide moiety. The muramic acid was replaced with a hydrophilic arene and lipophilic chain was introduced at peptide end to give the amphiphilic desmuramyl peptides (DMPs). The novel DMPs were found to modulate the immune response by amplifying the LPS-induced surface glycoprotein (ICAM-1) expression in THP-1 cells without showing significant toxicity. Furthermore, these compounds were able to trigger the secretion of higher levels of pro-inflammatory cytokine (TNF-α) than the well-studied NOD2 agonist, Murabutide.