Inflammation is the key factor in causing chronic degenerative diseases. There are unmet needs to treat inflammatory diseases; scientists are prompted to explore new anti-inflammatory compounds. Eugenol, 4-allyl-2-methoxy phenol, is a naturally occurring phenolic compound in Syzygium aromaticum (clove), Pimenta racemosa (bay leaves) and Cinnamomum verum (cinnamon leaf). It possesses a wide spectrum of biological activities, including anti-inflammatory, antimicrobial, antioxidant, analgesic, anticarcinogenic and anti-diabetic activities. However, eugenol has low solubility, undergoes degradation and exerts a toxic effect attributed to the presence of the free phenolic group of the molecule. The main objectives of this work are to synthesise new eugenol derivatives, investigate their anti-inflammatory activity, predict the molecular targets, and predict their drug-like properties using in silico studies. A total of twelve (12) eugenol derivatives were successfully synthesised and characterised using Ultra violet-visible (UV-Vis), Fourier-transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy. The cytotoxicity of the test compounds on murine macrophages (RAW 264.7 cells) was assessed using an MTT assay. Their anti-inflammatory activity was evaluated using Griess assay on LPSEc (Escherichia coli lipopolysaccharide) stimulated inflammation in RAW 264.7 cells. The effect of compounds in the gene and protein expression of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α and IFN-γ) were determined using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). All compounds were shown to be non-cytotoxic up to 10 μM in murine macrophage RAW 264.7 cells. The target compounds showed significant anti-inflammatory activity through the reversal of upregulation of the aforementioned cytokines. The absorption, distribution, metabolism, elimination and toxicity (ADMET) properties of the compounds were predicted in silico using Schrödinger Small Molecule Drug Discovery Suite software. The ADMET properties of the target compounds were predicted to be within the range of those of 95% of known drugs. Keywords: Eugenol, Synthesis, Anti-inflammatory, Cytotoxicity