In this study, we demonstrated the feasibility of nanostructured CuO thin film usage for caffeine sensing. Our morphological studies revealed that ellipse- or spiral-shaped nanostructured were formed with good crystal qualities. It was shown that the film thickness was decreased from 803 nm to 717 nm with annealing. Better crystalline quality of annealed films resulted in higher sensing response. Moreover, caffeine sensing response time was decreased to 19 s from 28 s for annealed films compared to as-grown CuO films. Both films exhibited excellent linearity with higher than 0.93 R2 values for the caffeine values from 0.5 mM to 10 mM, which is the range for most caffeinated hot and cold beverages. Caffeine is considered the only legal stimulant and its excessive use is not healthy. Knowing the caffeine content of beverages using portable, cheap sensor devices will be beneficial for the health-conscious society. We believe our sensing scheme in using nanostructured semiconductor thin films will pave the way to ultimately create advanced materials-based portable sensor devices.