Palladium nanoparticles (PdNPs) are of great important catalysts for a wide variety of applications. With the increasing demands of these materials, green and novel synthesis methods have become one of the leading research focuses. In obedience to the principle of an eco-friendly approach, PdNPs were developed following a one-pot green synthesis technique using sodium hyaluronate (SH) as reductant and stabilizer, which is a non-toxic, renewable, and glycosaminoglycan polymer. The synthesis protocol was spectroscopically monitored to achieve an optimum reaction condition using a one-variable-at-a-time technique where all parameters (concentration of SH, media pH, reaction time, and temperature) were tested in a set of experiments. The growth of PdNPs was evinced from intense brown color in the reaction solution and broad continuous absorption spectra in the UV–vis region. The synthesized PdNPs coated with SH-macromolecules were face-centered cubic crystal structure (d-spacing = 0.233 nm) with spherical/oval shape, uniformly polydispersed (ranged from 2.1 to 8.6 nm), smaller in size (5.3 ± 2.1 nm), and highly stabilized (zeta potential = −25.0 mV). The homogeneous catalytic performance of PdNPs exhibited almost 100% dye degradation for reactive red 195 and reactive yellow 145 by 12 and 16 min with a kinetic-constant value of 0.2128 and 0.1505 min –1 , respectively. The practical application of as-synthesized biogenic PdNPs as a nanocatalyst could be explored for the eco-friendly environmental treatment of wastewaters polluted with toxic, mutagenic, and hazardous azo dyes/pigments. • This bioreduction method is capable of synthesizing PdNPs by green and fast approach. • Hyaluronate is used as a soft matrix and reducing-stabilizing agent for PdNPs synthesis. • The high yield of the PdNPs is achieved using a one-variable-at-a-time optimization strategy. • Synthesized PdNPs are nano-sized, spherical shape, uniformly polydisperse, highly stable, and FFC crystal structure. • The synthesized PdNPs possessed excellent catalytic reduction potential against toxic azo dyes.