Objective: To systematically evaluate how different deep brain stimulation of the subthalamic nucleus (STN-DBS) amplitude, frequency, and pulse-width electrical parameter settings impact speech intensity, voice quality, and prosody of speech in Parkinson’s disease (PD). Methods: Ten individuals with PD receiving bilateral STN-DBS treatments were seen for three baseline and five treatment visits. The five treatment visits involved an examination of the standard clinical settings as well as manipulation of different combinations of frequency (low, mid, and high), pulse width (low, mid, and high), and voltage (low, mid, and high) of stimulation. Measures of speech intensity, jitter, shimmer, harmonics–noise ratio, semitone standard deviation, and listener ratings of voice quality and prosody were obtained for each STN-DBS manipulation. Results: The combinations of lower frequency, lower pulse width, and higher voltage settings were associated with improved speech outcomes compared to the current standard clinical settings. In addition, decreased total electrical energy delivered to the STN appears to be associated with speech improvements. Conclusions: This study provides preliminary evidence that STN-DBS may be optimized for Parkinson-related problems with voice quality, speech intensity, and prosody of speech.