<p>Traditional topical therapies can have considerable side effects, leading to the research for natural and biocompatible alternatives. Ectoine, a natural osmolyte produced by extremophilic microorganisms, possesses an extraordinary ability to bind water molecules and stabilize membranes, with powerful moisturizing and anti-inflammatory properties, which makes it a multifunctional and valuable molecule for topical applications. Pre-clinical and clinical data confirm that ectoine-based creams increase skin moisture, improve the skin’s barrier function, and reduce inflammation, effectively alleviating the symptoms of atopic dermatitis. In addition, ectoine can be used in nasal sprays, providing substantial relief from the symptoms of rhinosinusitis, such as nasal congestion and irritation of the mucous membranes, without the adverse effects associated with the usual decongestants. In ophthalmic formulations, ectoine-containing eye drops moisturize, stabilize the tear film, and relieve irritation and itching, making them a viable option for the ocular symptoms of allergic conjunctivitis and the long-term treatment of dry eye disease. Therefore, ectoine is crucial in developing treatments that improve patients’ quality of life by offering a safer alternative to conventional therapies.</p><p>Briefly, this review aims to explore the topical applications, characteristics, and mechanisms of action of ectoine, focusing on its efficacy and safety in the treatment of atopic dermatitis, rhinosinusitis, rhinitis sicca, dry eye disease, and allergic conjunctivitis. Moreover, biotechnological methods for producing ectoine are outlined, highlighting advances in microbial synthesis and process optimization for more sustainable technology, as well as showing ectoine-containing products and their position on the market.</p>