Dopamine (DA), as a neurotransmitter in human brain, plays a crucial role in reward motivation and motor control. An improper level of DA can be associated with neurological disorders such as schizophrenia and Parkinson’s disease. To quantify DA, optical DA sensors have emerged as an attractive platform due to their capability of high-precision and label-free measurement, and immunity to electromagnetic interference. However, the lack of selectivity, limited biocompatibility, and complex fabrication processes are challenges that hinder their clinical applications. Here, we report a soft and biocompatible luminescent hydrogel optical sensor capable of recognizing and quantifying DA with a simple and compact interrogation setup. The sensor is made of a hydrogel optical fiber (HOF) incorporated with upconversion nanoparticles (UCNPs). DA molecules are detected through the luminescence energy transfer (LET) between the UCNPs and the oxidation products of DA, while the light-guiding HOF enables both excitation and emission collection of the UCNPs. The hydrogel sensor provides an optical readout that shows a linear response up to 200 μmol/L with a detection limit as low as 83.6 nmol/L. Our results show that the UCNP-based hydrogel sensor holds great promise of serving as a soft and biocompatible probe for monitoring DA in situ.