Plaque biofilm is considered one of the etiological factors involved in the onset of caries and gingivitis, and is associated with the progression of periodontitis and peri-implant inflammation. There is no agreement in the literature on the effectiveness of the oscillating-rotating (OR) powered toothbrush (PTB) and high-frequency sonic (HFS) PTB in improving oral health. Thus, using the present proof-of-concept study we aimed to evaluate the effectiveness of OR PTB versus HFS PTB in terms of the improvement in plaque, gingival inflammation, and lingual patina indexes in dental hygiene university students. Dental hygiene students from the University of Eastern Piedmont “A. Avogadro” of Novara, Italy from November 2019 to October 2021 were recruited. Based on the type of toothbrush previously used for at-home plaque removal, the study participants were divided into two groups: Group 1 (subjects that used MTB prior to the study beginning, asked to use OR PTB for 2 times/day for a minimum of 3 months) and Group 2 (subjects that used HFS PTB prior to the study beginning). All the participants were instructed to avoid floss aids during the study (i.e., pipe cleaners, dental floss, and mouthwash). The outcome measures were: New Method of Plaque Scoring (NMPS), simplified Oral Disease Index (OHI-S), Plaque Control Record (PCR), Gingival Bleeding Index, and Winkel Tongue Coating Index (WTCI). All the outcomes were assessed at baseline (T0) in both groups and after 3 months (T1) in Group 1. Fifty-seven subjects (44 females and 13 males) were included and allocated to the study group (n = 30, 22 females and 8 males) and control group (n = 27, 22 females and 5 males). At T0, all the indexes were significantly higher in Group 2 (p < 0.0001). At T1, NMPS, OHI-S, PCR, GBI, and WTCI were statistically improved in Group 1 (p < 0.0001). Lastly, there was a statistically significant difference between Group 1 at T1 and Group 2 at T0 in terms of NMPS (p = 0.043), OHI-S (p = 0.032), and PCR (p < 0.001). Taken together, the findings of this proof-of-concept study showed the effectiveness over a 3-month period of both oscillating-rotating and sonic PTB in terms of oral health status in a sample of dental hygiene students.