Alzheimer’s disease (AD) is a neurological disorder whose treatment needs new therapies.1 Five sulfonamides derived from carvacrol,2 a natural small-molecule product with drug-like properties, were evaluated with respect to their effects on the cognitive deficits of animals with streptozotocin (STZ)-induced Alzheimer’s disease (AD). In vitro assays were performed using the acetylcholinesterase (AChE) and the data were combined with molecular modeling investigations for the establishment of structure-activity relationships (SAR). The memories of animals treated with compounds derived from morpholine (1), hydrazine (3) and 2-phenol (5) were improved. Compound 3 was the most promising, yielding excellent results in the inhibitory avoidance test. Moreover, the compounds did not exhibit any deleterious effects on the animals’ ambulation. In short, compounds 1, 3 and 5 can reduce STZ-induced deficits and show potential for the treatment of AD. These compounds produce significant anxiolytic and antioxidant effects and have favorable pharmacokinetics profile and drug-like properties.