The index closed 1.96 points lower after dropping 12.50 points in the previous session.
Trading on the Ho Chi Minh Stock Exchange decreased by 18% to VND12.843 trillion (US$523.1 million).
The VN-30 basket, comprising the 30 largest capped stocks, saw 14 tickers fell.
SSB of SeABank plummeted by 5.9%, followed by PLX of fuel distributor Petrolimex with a 1.3% drop and POW of electricity producer Petrovietnam Power Corporation, down 1.2%.
Eleven blue chips gained. STB of Ho Chi Minh City-based lender Sacombank went up 1.4%, HPG of steelmaker Hoa Phat Group gained 0.8%, and VJC of budget airline Vietjet closed 0.77% higher.
Foreign investors were net buyers to the tune of VND7 billion, mainly buying FPT of IT giant FPT Corporation and VNM of dairy giant Vinamilk.
The HNX-Index for stocks on the Hanoi Stock Exchange, home to mid and small caps, fell 0.10%, while the UPCoM-Index for the Unlisted Public Companies Market went down 0.05%.
MSCI's broadest index of Asia-Pacific shares outside Japan dropped 0.3%, Reuters reported.
U.S. stock futures faltered and the dollar was on the defensive on Wednesday, while bond prices rallied, as markets reacted to a U.S. presidential debate in which Vice President Kamala Harris put Republican Donald Trump on the defensive. S&P 500 futures eased 0.36%.
European shares were the bright spot, with the pan-European STOXX 600 index was edging up 0.07%, boosted by the oil and gas sectors on concerns that Hurricane Francine would disrupt output in the U.S.