In this study, the activity and structure of lysozyme were investigated in different ionic liquid formulations. Hen egg white lysozyme solutions were formulated in different ionic liquids with two additives. The ionic liquids studied were N‑ethyl‑N‑methylmorpholinium bromide, N‑butyl‑N‑methylmorpholinium bromide, N‑octyl‑N‑methylmorpholinium bromide, N‑benzyl‑N‑methyl‑morpholinium chloride, Benzyltriethylammonium Chloride, Triethylhexylammonium Bromide, and 1‑Ethyl‑3‑methylimidazolium ethyl sulfate. The additives used were carboxymethylcellulose and polyethylene glycol. All the formulations showed good protecting effect compared to buffer medium and some of the formulations enhanced the Lyz activity by ≈25%. Moreover, after 4 weeks of storage at room temperature, the protecting formula could retain more than 90% of the activity compared to the enzyme in the buffer which only retained ≈70%. This study not only provides the ILs efficiency in protecting enzyme activity but also recommends the use of a mixture of ionic liquids with polymers for further protein studies.