Luc Mbah a Moute has the highest plus-minus in a game, at +57 versus the Nuggets on November 22, 2017.

what is the best single game plus minus in a game ever
Interpreted as:
What is the best single game plus minus by a player in a regular-season game ever?
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11/22/2017Mbah a Moute4/2/2021Trent12/2/2021Aldama11/8/2001Smith3/22/2018Lamb11/30/2019Harden12/8/2018Theis10/31/2002Jeffries11/8/2001Szczerbiak5/1/2021Sabonis5/1/2021Brissett4/2/2021Siakam2/2/2009Stoudemire10/31/2002Lue4/19/1997Smith3/28/2016Mack1/1/2012Brewer12/2/2008Billups11/8/2001Brandon5/1/2021LeVert3/22/2018Walker3/22/2018Williams+57+54+52+52+51+50+50+50+50+49+49+49+49+49+49+48+48+48+48+47+47+47
NAMEDATETMOPP+/-MINPTSREBASTSTLBLKTOVFGMFGAFG%3PM3PA3P%FTMFTAFT%PF
Luc Mbah a MouteLuc Mbah a Moute11/22/2017HOUHOUvsDENDEN+5726134140255100.033100.0003
Gary Trent Jr.Gary Trent Jr.4/2/2021TORTORvsGSWGSW+5430245112081457.16966.722100.01
Santi AldamaSanti Aldama12/2/2021MEMMEMvsOKCOKC+52281810311081650.0030.02366.71
Joe SmithJoe Smith11/8/2001MINMINvsCHICHI+5227178310171070.0003475.02
Jeremy LambJeremy Lamb3/22/2018CHACHAvsMEMMEM+512612961034757.12450.022100.02
James HardenJames Harden11/30/2019HOUHOUvsATLATL+50316038315162466.781457.1202387.03
Daniel TheisDaniel Theis12/8/2018BOSBOS@CHICHI+50322210514081553.32450.04757.13
Jared JeffriesJared Jeffries10/31/2002WASWASvsBOSBOS+502912510015771.422100.0010.01
Wally SzczerbiakWally Szczerbiak11/8/2001MINMINvsCHICHI+502213230016875.011100.0001
Domantas SabonisDomantas Sabonis5/1/2021INDIND@OKCOKC+4930261914105101376.92366.74666.72
Oshae BrissettOshae Brissett5/1/2021INDIND@OKCOKC+49401613304161154.53650.01333.33
Pascal SiakamPascal Siakam4/2/2021TORTORvsGSWGSW+49313675200142458.34944.444100.02
Amar'e StoudemireAmar'e Stoudemire2/2/2009PHXPHXvsSACSAC+4928258010261250.0001313100.03
Tyronn LueTyronn Lue10/31/2002WASWASvsBOSBOS+493510550014850.02540.0002
Steve SmithSteve Smith4/19/1997ATLATLvsPHIPHI+4928214710091275.033100.0000
Shelvin MackShelvin Mack3/28/2016UTAUTAvsLALLAL+4829173500281172.71333.3000
Ronnie BrewerRonnie Brewer1/1/2012CHICHIvsMEMMEM+4835177520361060.011100.044100.02
Chauncey BillupsChauncey Billups12/2/2008DENDENvsTORTOR+48322411410181266.75683.333100.00
Terrell BrandonTerrell Brandon11/8/2001MINMINvsCHICHI+4823143124015955.60044100.00
Caris LeVertCaris LeVert5/1/2021INDIND@OKCOKC+4727251612191560.04666.733100.03
Kemba WalkerKemba Walker3/22/2018CHACHAvsMEMMEM+47284634102131872.2101471.41010100.01
Marvin WilliamsMarvin Williams3/22/2018CHACHAvsMEMMEM+472815602105862.52540.03475.00
Chris PaulChris Paul2/3/2018HOUHOU@CLECLE+47272281110081457.16966.7004
Darren CollisonDarren Collison2/19/2012INDINDvsCHACHA+472911261012633.311100.066100.00
Amar'e StoudemireAmar'e Stoudemire1/21/2007PHXPHXvsMINMIN+47282581110111478.60033100.03
StatMuse has game-level data for +/- going back to the 1996-97 season.