Arboviral diseases and malaria transmitted by mosquitoes are major health concerns worldwide responsible for millions of deaths annually. Spatial repellents have been used as preventative measures via direct application to the skin or disposable devices worn outside of clothing. Naturally derived, plant-based repellents are safe, effective alternatives to synthetic repellents and may be applied to disposable substrates including adhesive patches. Many disposables are composed of synthetic petrochemical-based polyester and polypropylene nonwoven fabrics, contributing to growing concern surrounding microplastic pollution. Sustainable and biodegradable substrates including those made from cotton are cost effective and environmentally friendly. Therefore, we explored the utilization of cotton-based substrates for the application of natural spatial and synthetic contact insect repellents. Cotton fibers used in the study were commercially available greige cotton, scoured and bleached greige cotton and reginned greige cotton motes, a value-added byproduct of the ginning process. Synthetic polyester and polypropylene were used for comparison. Thermogravimetric/derivative thermogravimetric analysis (TG/DTG) in combination with modulated differential scanning calorimetry (mDSC) were used to discern vaporization properties of repellents from the substrates. Retention times of repellents on the substrates were analyzed using a Fourier-transform infrared spectroscopy–focal plane array detector and compared with the TG/DTG and mDSC data. Mosquito landing assays confirmed the feasibility of using cotton-based substrates treated with plant-based spatial repellents as an effective and environmentally friendly alternative to synthetic materials.